Affinage

AQP5

Aquaporin-5 · UniProt P55064

Length
265 aa
Mass
28.3 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AQP5 is an apically localized membrane water channel that mediates transepithelial water movement in secretory and barrier epithelia, where it concentrates at apical membranes and secretory canaliculi of salivary acini, corneal epithelium, and type I pulmonary cells (PMID:9755069). Beyond water, it functions as a selective gas channel, conducting CO2 but not NH3 with higher CO2/NH3 selectivity than AQP1 (PMID:19273840), and forms mercury-sensitive functional water channels whose contribution to osmotic permeability depends on its membrane versus cytoplasmic distribution (PMID:29118028). Its surface delivery is dynamically gated: M3 muscarinic receptor activation drives Ca2+-dependent trafficking of AQP5 from intracellular lipid-raft vesicles to the apical membrane along microtubules (PMID:10600522, PMID:16107506), a process requiring caveolin-1 and TRPC1-mediated Ca2+ influx (PMID:23203809), while the NPA motif is required for membrane targeting and PKA phosphorylation of Ser156 in the cytoplasmic loop modulates trafficking and downstream signaling (PMID:18042467, PMID:19262015). At the apical membrane AQP5 physically partners with TRPV4 to enable hypotonicity-induced Ca2+ entry and regulatory volume decrease (PMID:16571723), with AQP2 to impair its surface localization (PMID:23326416), and with prolactin-inducible protein (PIP), which directs its apical distribution in salivary glands (PMID:34440877). AQP5 expression is controlled transcriptionally and epigenetically by GATA6/Sp1 with HDAC3 repression and p300 coactivation (PMID:28615712), by Dot1a-mediated H3K79 methylation (PMID:23326416), and by repressive pSTAT4 acting downstream of GPX4/lipid-ROS signaling (PMID:38574973), while protein levels are set post-translationally by lysosomal and autophagic degradation following parasympathetic denervation (PMID:18450949, PMID:20689061). AQP5 contributes to fluid secretion (its loss causing lacrimal dysfunction via ER stress and inflammation (PMID:35002213)), immune cell migration (PMID:27871297), and oncogenic behavior, where Ser156 phosphorylation links it to c-Src to promote invasion and transformation (PMID:18478076) and where AQP5 marks tumorigenic gastric stem cells driving WNT-driven invasive cancer (PMID:32025032). Missense mutations in AQP5 cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma (PMID:23830519).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 High

    Established where AQP5 protein resides in tissues, defining it as an apical water channel of secretory and barrier epithelia rather than a basolateral or ubiquitous one.

    Evidence Immunohistochemistry and immunoelectron microscopy across cornea, salivary gland, and lung

    PMID:9755069

    Open questions at the time
    • Localization alone does not establish water-transport function in situ
    • Does not address regulation of trafficking
  2. 1999 Medium

    Showed AQP5 localization is dynamic and that Ca2+ and microtubules drive its vesicle-to-membrane trafficking, reframing it as a regulated rather than constitutive channel.

    Evidence Immunofluorescence with β-adrenergic stimulation in rat parotid; live-cell trafficking in AQP5-transfected HSG cells with Ca2+ and cytoskeletal inhibitors

    PMID:10022971 PMID:10600522

    Open questions at the time
    • Receptor coupling not identified at this stage
    • Molecular machinery of vesicle docking unresolved
  3. 2000 High

    Tested whether AQP5 is non-redundantly required for fluid secretion in the lacrimal gland, finding it dispensable for pilocarpine-stimulated tear secretion.

    Evidence AQP5 knockout mice with in vivo tear volume measurement

    PMID:10870513

    Open questions at the time
    • Negative result may reflect compensation by other AQPs
    • Later work found other lacrimal phenotypes (#31)
  4. 2005 High

    Defined the upstream receptor signaling for AQP5 trafficking, showing M3 muscarinic and VIP/PKA pathways drive Ca2+-dependent apical insertion from lipid-raft vesicles.

    Evidence Detergent solubility, sucrose flotation, and microscopy in rat parotid duct cells; subcellular fractionation in duodenal Brunner's glands with kinase inhibitors

    PMID:15650134 PMID:16107506

    Open questions at the time
    • Direct link between receptor and vesicle machinery not mapped
    • Lipid-raft dissociation mechanism unresolved
  5. 2006 High

    Identified AQP5–TRPV4 as a functional complex coupling water permeability to osmosensing and regulatory volume decrease.

    Evidence Reciprocal co-IP, AQP5-/- and TRPV4-/- mice, electrophysiology, Ca2+ imaging, N-terminal deletion mutant

    PMID:16571723

    Open questions at the time
    • Structural basis of the interaction not defined
    • Whether the complex forms in non-salivary tissues unknown
  6. 2007 Medium

    Dissected the roles of conserved motifs, showing the NPA motif is required for membrane targeting whereas PKA phosphorylation of Ser156 does not control basal trafficking.

    Evidence Site-directed mutagenesis (N185D, S156A) and PKA pharmacology in BEAS-2B cells

    PMID:18042467

    Open questions at the time
    • Functional role of Ser156 phosphorylation left open here
    • Single cell-type system
  7. 2008 Medium

    Connected AQP5 to oncogenic signaling, showing Ser156 phosphorylation and membrane trafficking are required for c-Src binding, invasion, EMT, proliferation, and transformation.

    Evidence Mutagenesis with invasion/transformation assays, SH3 protein array, and IP in BEAS-2B/NIH3T3 and CML cells

    PMID:18423983 PMID:18478076 PMID:18612408

    Open questions at the time
    • Mechanistic link between a water channel and kinase signaling not fully explained
    • Single-lab cell-line studies
  8. 2009 Medium

    Established AQP5 as a selective CO2 channel and refined the phosphorylation-trafficking relationship, showing dephosphorylation of the PKA motif promotes microtubule-dependent apical targeting.

    Evidence Surface pH and Pf measurements in Xenopus oocytes; GFP-AQP5 mutant trafficking in MDCK-II cells

    PMID:19262015 PMID:19273840

    Open questions at the time
    • Physiological significance of CO2 conduction in vivo not established
    • Phosphatase responsible for dephosphorylation unidentified
  9. 2010 Medium

    Defined inflammatory and degradative regulation, showing LPS represses AQP5 transcription via NF-κB/AP-1 and that denervation triggers lysosomal/autophagic AQP5 degradation.

    Evidence In vivo LPS in TLR4-mutant mice with co-IP and promoter binding; denervation with LC3B-II, LAMP2 colocalization and cathepsin inhibitor assays

    PMID:20522648 PMID:20689061

    Open questions at the time
    • Direct ubiquitin/autophagy adaptor for AQP5 not identified
    • Promoter binding assays were not full ChIP
  10. 2011 Medium

    Extended AQP5 biology to disease and unexpected tissue, linking impaired cevimeline-induced trafficking to diabetic xerostomia and identifying AQP5 in renal type-B intercalated cells.

    Evidence STZ-diabetic rat parotid fractionation and immunohistochemistry; multi-species kidney immunocytochemistry

    PMID:21295117 PMID:22178880

    Open questions at the time
    • Renal osmosensory role inferred, not functionally tested
    • Insulin rescue mechanism unresolved
  11. 2013 High

    Uncovered epigenetic transcriptional repression by Dot1a/H3K79 methylation, an AQP5–AQP2 inhibitory interaction, hypoxic HIF-1α repression, and a causative human disease link.

    Evidence Reporter, ChIP, co-IP and conditional Dot1l KO mice; hypoxia/cobalt with DN-HIF-1α and proteasome inhibitors; exome sequencing of palmoplantar keratoderma families

    PMID:23326416 PMID:23469202 PMID:23830519

    Open questions at the time
    • Functional channel consequence of keratoderma mutations not measured
    • How AQP5 retains AQP2 intracellularly mechanistically unclear
  12. 2014 Medium

    Placed AQP5 upstream of stress-MAPK signaling in cancer drug resistance, with knockdown sensitizing colon cancer cells to chemotherapy.

    Evidence siRNA knockdown with viability, drug-resistance protein, and p38 MAPK epistasis in HT-29 cells

    PMID:24752576

    Open questions at the time
    • Direct molecular link between AQP5 and p38 unknown
    • Single cell line
  13. 2015 Medium

    Demonstrated lens water-channel function and nuclear/lateral trafficking, showing AQP5's measurable permeability contribution depends on membrane insertion and that it can localize to the nuclear membrane.

    Evidence Membrane vesicle Pf with Hg2+ inhibition in lens; immunoconfocal/EM and nuclear fractionation in rat parotid

    PMID:25603543 PMID:29118028

    Open questions at the time
    • Functional role of nuclear AQP5 beyond nuclear size change unclear
    • Species differences in distribution mechanistically unexplained
  14. 2016 Medium

    Established AQP5 as a promoter of immune cell migration, with knockout improving LPS survival and overexpression enhancing chemotactic migration.

    Evidence Aqp5 KO mouse LPS survival, neutrophil counts, and human/Jurkat migration assays

    PMID:27871297

    Open questions at the time
    • Mechanism linking water transport to migration not defined
    • Genotype association is correlative
  15. 2017 Medium

    Resolved the GATA6/Sp1/HDAC3/p300 transcriptional circuit governing AQP5 and extended AQP5–MAPK signaling to glioma and corneal inflammation.

    Evidence Reporter, ChIP, co-IP and gain/loss-of-function for transcription factors; siRNA and MAPK pharmacology in glioma and corneal epithelial cells

    PMID:28404978 PMID:28615712 PMID:28680052

    Open questions at the time
    • How AQP5 mechanistically engages EGFR/ERK/p38 unresolved
    • Inflammation findings tissue-specific
  16. 2020 High

    Identified AQP5 as a marker of pyloric stem cells with cancer stem cell activity, providing in vivo evidence it labels the origin of WNT-driven invasive gastric cancer.

    Evidence Aqp5-creERT2 lineage tracing, organoid assays, and prospective isolation in mouse and human stomach

    PMID:32025032

    Open questions at the time
    • Whether AQP5 channel activity is functionally required for stemness not tested here
    • Causal driver versus marker distinction
  17. 2021 Medium

    Characterized PIP as a direct AQP5 partner controlling apical localization and defined additional knockout phenotypes in lacrimal gland and lens.

    Evidence Co-IP with domain mapping and PIP-KO mice; AQP5-/- ER stress/inflammation analysis; CRISPR AQP5 KO with miR-124-3p.1/vimentin luciferase validation

    PMID:33582182 PMID:34440877 PMID:35002213

    Open questions at the time
    • How PIP binding directs trafficking mechanistically unresolved
    • Link between AQP5 loss and miR-124-3p.1 downregulation indirect
  18. 2022 Medium

    Connected AQP5 to autophagy-driven gastric cancer stemness via TRIM21-mediated K63 ubiquitination of ULK1 and cooperation with LGR5.

    Evidence Single-cell/proteomic profiling, mass spectrometry, co-IP, ubiquitination and tumorigenesis assays

    PMID:36372898

    Open questions at the time
    • How AQP5 recruits TRIM21 to ULK1 not structurally defined
    • Single-lab cancer model
  19. 2024 High

    Established a GPX4/lipid-ROS/STAT4 axis directly repressing AQP5 transcription, linking ferroptotic redox stress to impaired salivary secretion.

    Evidence GPX4 gain/loss-of-function, ChIP of pSTAT4 at the AQP5 promoter, ferrostatin-1, and in vivo Sjögren model

    PMID:38574973

    Open questions at the time
    • Whether this axis operates in non-salivary tissues unknown
    • Upstream trigger of GPX4 reduction not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AQP5's water/CO2-conducting activity is mechanistically coupled to its signaling, migration-promoting, and cancer-stem-cell roles remains unresolved.
  • No structural model integrating channel and protein-interaction functions
  • Whether transport activity is required for oncogenic roles untested
  • Cross-tissue generality of regulatory circuits unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 2 GO:0140104 molecular carrier activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 2 GO:0031410 cytoplasmic vesicle 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2 R-HSA-382551 Transport of small molecules 2 R-HSA-9612973 Autophagy 2
Partners
AQP2CAV1PIPSRCTRIM21TRPV4

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 AQP5 protein is selectively localized to the apical membranes of corneal epithelial surface cells, acinar cell apical membranes and microvilli of intracellular secretory canaliculi in serous salivary glands, and apical membranes of type I pulmonary epithelial cells, as established by immunohistochemistry and immunoelectron microscopy. Immunohistochemistry and immunoelectron microscopy with affinity-purified anti-AQP5 antibody The American journal of physiology High 9755069
1999 AQP5 protein in rat salivary glands is restricted to apical membranes including intercellular secretory canaliculi of acinar cells; upon isoproterenol (β-adrenergic) stimulation, apical AQP5 staining in parotid acinar cells redistributes to clustered dot patterns, suggesting dynamic membrane redistribution. Immunofluorescence microscopy with anti-AQP5 antibody; pharmacological stimulation with isoproterenol Cell and tissue research Medium 10022971
1999 AQP5 trafficking from intracellular vesicles to the plasma membrane requires elevation of intracellular Ca2+ (triggered by thapsigargin or Ca2+ ionophore A-23187) and depends on intact microtubules (colchicine/vinblastine sensitive) but is not completely inhibited by microfilament disruption (cytochalasin B). Confocal laser microscopy of AQP5-transfected HSG cells with pharmacological inhibitors of Ca2+ and cytoskeletal components Biochemical and biophysical research communications Medium 10600522
2000 AQP5 knockout mice do not show significantly reduced pilocarpine-stimulated tear secretion, providing direct experimental evidence against an essential non-redundant role for AQP5 in lacrimal gland fluid secretion. Knockout mouse model; in vivo tear volume measurement with microcapillary tubes before and after pilocarpine Experimental eye research High 10870513
2005 M3 muscarinic acetylcholine receptor activation (by cevimeline or Ca2+ ionophore A-23187) induces AQP5 trafficking from intracellular lipid raft-containing vesicles to the apical plasma membrane in rat parotid interlobular duct cells, followed by dissociation of AQP5 from lipid rafts on the apical membrane; this process is Ca2+-dependent. Immunofluorescence/immunoelectron microscopy, detergent solubility assay, discontinuous sucrose density gradient flotation, confocal microscopy American journal of physiology. Cell physiology High 16107506
2005 Vasoactive intestinal polypeptide (VIP) induces translocation of AQP5 (but not AQP1) to the apical membrane in rat duodenal Brunner's gland cells via a PKA-dependent (H-89-sensitive), PKC-independent mechanism. Subcellular fractionation of duodenal slices, Western blot, immunohistochemistry; pharmacological inhibitors H-7, H-89, calphostin C; in vivo VIP injection American journal of physiology. Gastrointestinal and liver physiology High 15650134
2006 AQP5 and TRPV4 form a physical complex at the apical membrane of salivary acinar cells; AQP5 is required for hypotonicity-induced TRPV4 activation and regulatory volume decrease (RVD). Deletion of the AQP5 N-terminus suppresses TRPV4 activation and RVD. Hypotonicity increases co-association and surface expression of both proteins, effects blocked by actin depolymerization. Co-immunoprecipitation, knockout mice (AQP5-/- and TRPV4-/-), electrophysiology, Ca2+ imaging, cell volume measurements, N-terminal deletion mutant expression The Journal of biological chemistry High 16571723
2007 In AQP5-transfected bronchial epithelial cells, serine-156 (the PKA consensus site) is phosphorylated by PKA; the S156A mutant abolishes this phosphorylation. However, PKA phosphorylation of S156 does not regulate membrane targeting of AQP5. The N185D (NPA motif) mutant localizes predominantly to cytoplasm rather than apical membrane, indicating the NPA motif is required for membrane targeting. Stable transfection of BEAS-2B cells grown on permeable supports; phosphorylation assay; immunofluorescence; pharmacological PKA inhibition/activation (H89, cpt-cAMP) Biochemical and biophysical research communications Medium 18042467
2008 AQP5 requires membrane trafficking (N185D NPA-motif mutation blocks this) and phosphorylation on Ser156 (S156A mutant blocks this) for promoting cell invasion and epithelial-to-mesenchymal transition. AQP5 (but not mutants) binds activated c-Src (phospho-Tyr416) via SH3 domain interaction, as shown by protein array and immunoprecipitation, and induces spindle-like morphology and loss of epithelial markers. Stable transfection of BEAS-2B and NIH3T3 cells; in vitro invasion assay; SH3-domain protein array; immunoprecipitation; site-directed mutagenesis (N185D, S156A) PloS one Medium 18478076
2008 AQP5 overexpression in K562 CML cells increases BCR-ABL1 phosphorylation, while AQP5 siRNA knockdown decreases BCR-ABL1 phosphorylation and increases caspase-9 activity, indicating AQP5 promotes proliferation and inhibits apoptosis partly through BCR-ABL1 signaling. Overexpression and siRNA knockdown in K562/LAMA84 cells; immunoblotting for BCR-ABL1 phosphorylation; flow cytometry caspase-9 activity assay; proliferation assay PloS one Medium 18612408
2008 AQP5 overexpression promotes oncogenic transformation and cell proliferation in a manner dependent on PKA-mediated phosphorylation of the Ser156 cAMP/PKA consensus site in its cytoplasmic loop. Ectopic expression of wild-type and PKA-site mutant AQP5 in cell lines; proliferation and transformation assays in vitro and in vivo Cancer letters Medium 18423983
2008 Parasympathetic (chorda tympani) denervation of rat submandibular gland reduces AQP5 protein level to ~37% of control without affecting AQP5 mRNA, indicating post-transcriptional/protein-level regulation. Cevimeline (M3 mAChR agonist) but not pilocarpine restores this loss; chloroquine (lysosomal inhibitor) prevents AQP5 degradation, and lysosomal extracts degrade AQP5 in vitro, implicating lysosomal degradation. Surgical denervation (parasympathectomy/sympathectomy); Western blot; RT-PCR; pharmacological rescue (cevimeline, pilocarpine, chloroquine); in vitro degradation assay with lysosomal fractions American journal of physiology. Gastrointestinal and liver physiology High 18450949
2009 AQP5 conducts CO2 across cell membranes (as assessed by surface pH changes in Xenopus oocytes) but does not conduct NH3, exhibiting a higher CO2-to-NH3 selectivity ratio than AQP1 or AmtB. Surface pH measurements in Xenopus oocytes expressing rat AQP5; comparison with H2O-injected controls and other channels; osmotic water permeability (Pf) measurements Proceedings of the National Academy of Sciences of the United States of America High 19273840
2009 GFP-AQP5 mutants with unphosphorylatable substitutions at the PKA consensus motif (152SRRTS) show 1.5–2× greater translocation to the apical membrane in MDCK-II cells compared to wild-type GFP-AQP5, and this translocation is microtubule-dependent (colchicine-sensitive) but microfilament-independent (cytochalasin B-insensitive), indicating dephosphorylation of S152 promotes membrane targeting via microtubule-dependent transport. GFP-AQP5 chimeric protein expression in MDCK-II cells; site-directed mutagenesis of PKA motif; confocal microscopy; pharmacological inhibition (H-89, colchicine, cytochalasin B) The journal of medical investigation : JMI Medium 19262015
2010 LPS-induced downregulation of AQP5 mRNA in the parotid gland is mediated via activation of NF-κB and p-c-Jun/c-Fos (AP-1), which form a physical complex as shown by co-immunoprecipitation; specific kinase inhibitors for IKK, ERK1/2, JNK, and p38 MAPK each block LPS-induced AQP5 downregulation. In vivo LPS injection in TLR4-mutant and wild-type mice; pharmacological inhibitors; co-immunoprecipitation; gel-shift/binding assays on AQP5 promoter sequences; RT-PCR; Western blot The American journal of pathology Medium 20522648
2010 Following chorda tympani denervation, AQP5 protein in rat submandibular gland is degraded via lysosomal/autophagosomal pathways: LC3B-II (autophagosome marker) is transiently induced, AQP5 co-localizes with LAMP2 and LC3 in acinar cells, cathepsins B and L are identified as candidate degrading enzymes by inhibitor experiments. Immunohistochemistry, co-localization, TUNEL assay, Western blot for autophagy markers (LC3B-II, LAMP2, Bax, Bcl-2); in vitro AQP5-degrading activity assay with lysosomal fraction and protease inhibitors American journal of physiology. Gastrointestinal and liver physiology Medium 20689061
2011 In streptozotocin-diabetic rats, M3 mAChR agonist cevimeline fails to induce AQP5 translocation to the apical plasma membrane of parotid acinar and duct cells (unlike in controls), and AQP5 protein is downregulated despite increased mRNA, contributing to diabetic xerostomia; insulin restoration tends to rescue cevimeline-induced AQP5 translocation. Western blot of subcellular fractions, immunohistochemistry, real-time PCR, detergent solubility assay in parotid glands of STZ-diabetic and insulin-treated rats Biochimica et biophysica acta Medium 21295117
2011 AQP5 is expressed at the apical membrane of type-B intercalated cells (co-localizing with pendrin) throughout the collecting duct system in rat, mouse, and human kidney cortex; no basolateral AQP is detected in these cells, suggesting AQP5 is not involved in net transepithelial water reabsorption but may serve an osmosensory role. Immunocytochemistry with segment- and cell-type-specific markers (pendrin, V-type H+-ATPase) in human, rat and mouse kidney sections Cellular physiology and biochemistry Medium 22178880
2012 Caveolin-1 (Cav1) is required for agonist-stimulated apical targeting and surface expression of AQP5 in salivary gland acinar cells; in Cav1-/- mice, AQP5 apical localization is disrupted and agonist-induced AQP5 surface expression is reduced. TRPC1-mediated Ca2+ influx is necessary for agonist-stimulated AQP5 surface expression. Adenoviral re-expression of Cav1 restores normal AQP5 apical targeting and fluid secretion. Cav1 knockout mice; adenoviral Cav1 rescue; Ca2+ imaging; surface biotinylation; immunofluorescence; co-IP of TRPC1-STIM1 Journal of cell science High 23203809
2013 Dot1a (histone H3 K79 methyltransferase) represses AQP5 transcription; deletion of Dot1l in renal Aqp2-expressing cells markedly upregulates Aqp5. Human AQP5 physically interacts with AQP2 (co-IP) and impairs AQP2 cell surface localization; the AQP5/AQP2 complex partially resides in the ER/Golgi. Luciferase reporter and chromatin assays confirm Dot1a/H3 dimethyl-K79 association with the Aqp5 5' flanking region. cDNA array, real-time RT-qPCR, luciferase reporter assay, cell surface biotinylation, co-immunoprecipitation, colocalization, ChIP-like assays; conditional Dot1l knockout mice PloS one High 23326416
2013 Missense mutations in AQP5 cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma; immunofluorescence shows mutant AQP5 proteins traffic normally to the plasma membrane in stratum granulosum, suggesting the mutations alter channel regulation rather than trafficking. Exome sequencing; protein structure analysis; immunofluorescence of patient palmar epidermis American journal of human genetics Medium 23830519
2013 Hypoxia decreases AQP5 expression in mouse lung (~70%) via HIF-1α-dependent transcriptional repression; dominant-negative HIF-1α and HIF-1α siRNA block cobalt-induced AQP5 downregulation. Proteasome inhibitors abolish both hypoxia- and cobalt-induced AQP5 reduction at mRNA and protein level, implicating proteasome-dependent stabilization of HIF-1α and possibly other transcription factors. Hypoxia chamber experiments in mice; MLE-12 cell line; dominant-negative HIF-1α and HIF-1α siRNA; proteasome inhibitors (lactacystin, PI-III); hnRNA real-time PCR PloS one Medium 23469202
2014 AQP5 knockdown in HT-29 colon cancer cells increases p38 MAPK phosphorylation and enhances sensitivity to 5-FU and cisplatin, while decreasing expression of multidrug resistance proteins P-gp, GST-π, and TOPO II; p38 MAPK inhibitor phenocopies AQP5 knockdown, placing AQP5 upstream of p38 MAPK in drug resistance signaling. siRNA knockdown; cell viability assay (SRB); Western blot and RT-PCR for drug resistance factors and MAPK pathway components Tumour biology Medium 24752576
2015 AQP5 forms functional, mercury-sensitive water channels in rodent lens fiber cells; the species-specific subcellular distribution (membranous in mouse, predominantly cytoplasmic in rat cortical fiber cells) determines whether AQP5 contributes measurably to osmotic water permeability (Pf). Organ culture causes insertion of rat AQP5 into cortical fiber membranes with a corresponding increase in Hg2+-sensitive Pf. Fluorescence dye dilution water permeability assay of membrane vesicles; HgCl2 inhibition; immunolabeling of lens sections and vesicles; organ culture American journal of physiology. Cell physiology Medium 29118028
2015 Muscarinic receptor activation in rat parotid acinar cells induces AQP5 translocation not only to the apical plasma membrane and lateral plasma membrane, but also to the nucleus and nuclear membrane; nuclear AQP5 is present in both soluble and insoluble nuclear fractions; nuclear size decreases when AQP5 is present in the nuclear membrane, suggesting AQP5 facilitates water movement across the nuclear membrane. Immunoconfocal and immunoelectron microscopy; Western blot of isolated nuclear and nuclear membrane fractions; sucrose-density flotation; detergent solubility assays; pharmacological (atropine) blocking Biochimica et biophysica acta Medium 25603543
2016 Aqp5 knockout mice have significantly higher survival (56% vs 22%) after LPS injection compared to wild-type, with reduced neutrophil migration into peritoneum and lung; conversely, AQP5-overexpressing Jurkat cells show 2.4× greater SDF-1α-stimulated migration and neutrophils from AA-genotype (higher AQP5) individuals migrate faster than AC/CC-genotype cells, establishing AQP5 as a promoter of immune cell migration. Aqp5 knockout mice; LPS survival experiment; peritoneal/lung neutrophil counting; filter migration assay of human neutrophils; AQP5-overexpressing Jurkat cell migration; AQP5 expression after fMLP by RT-PCR/Western blot Journal of translational medicine Medium 27871297
2017 GATA6 and Sp1 cooperatively activate Aqp5 transcription in alveolar type I cells; HDAC3 represses this activation by binding Sp1 and deacetylating histone H3 (not H4) at the Aqp5 promoter/enhancer; the co-activator/HAT p300 promotes Aqp5 expression by interacting with GATA6 and Sp1 and modulating H3 acetylation. HDAC inhibitor (SAHA) treatment; HDAC3 overexpression and knockdown; GATA6 and p300 knockdown/overexpression; luciferase reporter assays; ChIP-H3/H4 acetylation; co-IP of GATA6/Sp1/p300/HDAC3 Scientific reports High 28615712
2017 AQP5 knockdown in glioma cells (U87-MG, U251, LN229) reduces proliferation, increases apoptosis, suppresses migration, and decreases expression and phosphorylation of ERK1/2 and p38 MAPK but not JNK or AKT, placing AQP5 upstream of EGFR/ERK/p38 MAPK signaling. siRNA knockdown and overexpression; MTT proliferation assay; flow cytometry (apoptosis, cell cycle); scratch migration assay; Western blot for EGFR/ERK/p38 MAPK pathway proteins Oncotarget Medium 28404978
2017 Hyperosmolarity-induced AQP5 upregulation in human corneal epithelial cells mediates increases in proinflammatory cytokine expression (IL-1β, IL-6, IL-8, TNF-α, caspase-1) and cell death through JNK1/2 MAPK activation; siRNA silencing of AQP5 or pharmacological JNK inhibition (SP600125) reduces these effects. siRNA AQP5 knockdown; Western blot; TUNEL assay; JNK inhibitor SP600125; real-time RT-PCR in primary and cell-line human corneal epithelial cells Scientific reports Medium 28680052
2020 AQP5 marks pyloric stem cells in mouse and human stomach; Aqp5-creERT2 lineage tracing demonstrates that AQP5+ stem cells are a source of WNT-driven invasive gastric cancer in vivo; tumor-resident AQP5+ cells preferentially initiate organoid growth in vitro, indicating cancer stem cell activity. Comparative transcriptional profiling; Aqp5-creERT2 knock-in mouse model; lineage tracing; organoid growth assay; flow cytometry prospective isolation Nature High 32025032
2021 Prolactin-inducible protein (PIP) physically interacts with AQP5 in vitro, in mouse and human salivary glands; the interaction involves the AQP5 C-terminus and N-terminal domain of PIP (one PIP per AQP5 tetramer); PIP knockout mice show altered AQP5 distribution at the apical membrane of acinar cells, demonstrating PIP regulates AQP5 localization in salivary glands. Co-immunoprecipitation in vitro and from tissues; structural/interaction domain mapping; immunofluorescence of PIP-knockout mouse salivary glands and human minor salivary gland biopsies Cells High 34440877
2021 AQP5 knockout in mice causes AQP5 loss-associated lacrimal gland dysfunction via ER stress induction, lipid accumulation, and inflammatory chemokine upregulation (CXCL1, CXCL2, CCL5), reducing aqueous tear secretion by ~50%; quercetin treatment partially reverses ER stress and inflammation. AQP5-/- mice; TEM of ER structure; Western blot and qRT-PCR for ER stress markers, lipid metabolism genes, chemokines; Oil Red O staining; quercetin pharmacological intervention Molecular vision Medium 35002213
2021 AQP5 loss-of-function (AQP5 knockout or L51P missense mutation) in mouse lens leads to mild lens opacity associated with downregulation of miR-124-3p.1 and consequent upregulation of vimentin (a direct miR-124-3p.1 target confirmed by dual-luciferase reporter assay); miR-124-3p.1 agomir reduces lens opacity and vimentin in both WT and AQP5-KO mice. CRISPR/Cas9 AQP5 knockout mice; whole exome sequencing (human family); dual-luciferase reporter assay; qRT-PCR, Western blot, immunofluorescence; organ culture; miR agomir treatment Experimental eye research Medium 33582182
2022 AQP5 promotes gastric cancer stem cell (GC-CSC) tumorigenesis by activating autophagy (LC3I/LC3II conversion) and recruiting the E3 ubiquitin ligase TRIM21 to ULK1, inducing K63-linked ubiquitination of ULK1; AQP5 cooperates with LGR5 to synergistically promote GC-CSC malignant functions. Single-cell sequencing; transcriptome and proteomic analysis; mass spectrometry; co-IP; ubiquitination assay; sphere formation, proliferation, invasion, and in vivo tumorigenesis assays Journal of experimental & clinical cancer research : CR Medium 36372898
2024 In salivary gland epithelial cells, reduced GPX4 leads to lipid ROS accumulation, which activates STAT4 phosphorylation and nuclear translocation; pSTAT4 binds the AQP5 promoter (confirmed by ChIP assay) and suppresses AQP5 transcription, reducing salivary secretion. GPX4 overexpression reverses this cascade. GPX4 overexpression/knockdown; ChIP assay for pSTAT4 at AQP5 promoter; lipid ROS inhibitor ferrostatin-1; in vivo SS mouse model; Western blot; immunofluorescence Free radical biology & medicine High 38574973

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Relative CO2/NH3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG. Proceedings of the National Academy of Sciences of the United States of America 208 19273840
2006 A role for AQP5 in activation of TRPV4 by hypotonicity: concerted involvement of AQP5 and TRPV4 in regulation of cell volume recovery. The Journal of biological chemistry 194 16571723
2000 Decreased expression of aquaporin (AQP)1 and AQP5 in mouse lung after acute viral infection. American journal of respiratory cell and molecular biology 183 10615063
1999 Aquaporin-5 (AQP5), a water channel protein, in the rat salivary and lacrimal glands: immunolocalization and effect of secretory stimulation. Cell and tissue research 160 10022971
2003 Distribution of aquaporin water channels AQP1 and AQP5 in the ductal system of the human pancreas. Gut 137 12801959
1998 Localization and expression of AQP5 in cornea, serous salivary glands, and pulmonary epithelial cells. The American journal of physiology 135 9755069
2008 Expression of aquaporin 5 (AQP5) promotes tumor invasion in human non small cell lung cancer. PloS one 128 18478076
2020 AQP5 enriches for stem cells and cancer origins in the distal stomach. Nature 110 32025032
2005 Identification of AQP5 in lipid rafts and its translocation to apical membranes by activation of M3 mAChRs in interlobular ducts of rat parotid gland. American journal of physiology. Cell physiology 104 16107506
2000 Tear secretion by lacrimal glands in transgenic mice lacking water channels AQP1, AQP3, AQP4 and AQP5. Experimental eye research 96 10870513
2008 Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation. Cancer letters 82 18423983
2011 Localization of AQP5 during development of the mouse submandibular salivary gland. Journal of molecular histology 70 21203896
2013 Mutations in AQP5, encoding a water-channel protein, cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma. American journal of human genetics 69 23830519
2013 AQP5 expression predicts survival in patients with early breast cancer. Annals of surgical oncology 63 24114055
2011 Tanshinone IIA ameliorates seawater exposure-induced lung injury by inhibiting aquaporins (AQP) 1 and AQP5 expression in lung. Respiratory physiology & neurobiology 60 21244858
2011 Anti-asthmatic agents alleviate pulmonary edema by upregulating AQP1 and AQP5 expression in the lungs of mice with OVA-induced asthma. Respiratory physiology & neurobiology 57 22226856
2008 Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML). PloS one 57 18612408
2013 Aqp5 is a new transcriptional target of Dot1a and a regulator of Aqp2. PloS one 54 23326416
2020 Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions. International journal of molecular sciences 53 32053992
2012 Expression of AQP5 and AQP8 in human colorectal carcinoma and their clinical significance. World journal of surgical oncology 52 23148732
2012 Impairment of TRPC1-STIM1 channel assembly and AQP5 translocation compromise agonist-stimulated fluid secretion in mice lacking caveolin1. Journal of cell science 52 23203809
2002 Expression and localization of AQP5 in the stomach and duodenum of the rat. Biochimica et biophysica acta 52 11853885
2010 Potential down-regulation of salivary gland AQP5 by LPS via cross-coupling of NF-kappaB and p-c-Jun/c-Fos. The American journal of pathology 51 20522648
1999 Cloning and characterization of murine Aqp5: evidence for a conserved aquaporin gene cluster. Mammalian genome : official journal of the International Mammalian Genome Society 51 10337625
2007 Membrane trafficking of AQP5 and cAMP dependent phosphorylation in bronchial epithelium. Biochemical and biophysical research communications 50 18042467
2006 Decreased saliva secretion and down-regulation of AQP5 in submandibular gland in irradiated rats. Radiation research 50 16802868
2020 Exosomes co-expressing AQP5-targeting miRNAs and IL-4 receptor-binding peptide inhibit the migration of human breast cancer cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 49 31922312
2014 AQP5 silencing suppresses p38 MAPK signaling and improves drug resistance in colon cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 49 24752576
2005 Subcellular redistribution of AQP5 by vasoactive intestinal polypeptide in the Brunner's gland of the rat duodenum. American journal of physiology. Gastrointestinal and liver physiology 49 15650134
2017 Hyperosmolarity-induced AQP5 upregulation promotes inflammation and cell death via JNK1/2 Activation in human corneal epithelial cells. Scientific reports 48 28680052
2023 NNMT enriches for AQP5+ cancer stem cells to drive malignant progression in early gastric cardia adenocarcinoma. Gut 47 36977555
2003 Immunolocalization of the water channel, aquaporin-5 (AQP5), in the rat digestive system. Archives of histology and cytology 46 14692686
1999 Identification of aquaporin 5 (AQP5) within the cochlea: cDNA cloning and in situ localization. Biochemical and biophysical research communications 46 10527857
2016 Abnormal distribution of AQP5 in labial salivary glands is associated with poor saliva secretion in patients with Sjögren's syndrome including neuromyelitis optica complicated patients. Modern rheumatology 45 26375433
1999 Involvement of vesicle-cytoskeleton interaction in AQP5 trafficking in AQP5-gene-transfected HSG cells. Biochemical and biophysical research communications 44 10600522
2015 NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression. Biochemical and biophysical research communications 43 26299924
2011 AQP5 is expressed in type-B intercalated cells in the collecting duct system of the rat, mouse and human kidney. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 43 22178880
2022 AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination. Journal of experimental & clinical cancer research : CR 38 36372898
2017 AQP5 promotes hepatocellular carcinoma metastasis via NF-κB-regulated epithelial-mesenchymal transition. Biochemical and biophysical research communications 37 28619511
2005 A mouse caries model and evaluation of aqp5-/- knockout mice. Caries research 37 16251788
2002 Decreased expression of AQP1 and AQP5 in acute injured lungs in rats. Chinese medical journal 37 12150721
2016 Emodin ameliorates acute lung injury induced by severe acute pancreatitis through the up-regulated expressions of AQP1 and AQP5 in lung. Clinical and experimental pharmacology & physiology 35 27452155
2017 Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway. Oncotarget 34 28404978
2008 Upregulation of AQP3 and AQP5 induced by dexamethasone and ambroxol in A549 cells. Respiratory physiology & neurobiology 34 18280225
2013 Expression of aquaporin 5 and the AQP5 polymorphism A(-1364)C in association with peritumoral brain edema in meningioma patients. Journal of neuro-oncology 33 23392848
2009 Correlation between salivary secretion and salivary AQP5 levels in health and disease. The journal of medical investigation : JMI 32 20224222
2013 AQP5 is differentially regulated in astrocytes during metabolic and traumatic injuries. Glia 31 23922257
2015 Dexmedetomidine alleviates pulmonary edema by upregulating AQP1 and AQP5 expression in rats with acute lung injury induced by lipopolysaccharide. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 30 26489622
2012 E2f1-deficient NOD/SCID mice have dry mouth due to a change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland. Pflugers Archiv : European journal of physiology 30 23179381
1997 Closely spaced tandem arrangement of AQP2, AQP5, and AQP6 genes in a 27-kilobase segment at chromosome locus 12q13. Genomics 30 9268644
2017 Cell-specific expression of aquaporin-5 (Aqp5) in alveolar epithelium is directed by GATA6/Sp1 via histone acetylation. Scientific reports 28 28615712
2017 Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells. American journal of physiology. Cell physiology 28 29118028
2007 Interleukin-13 interferes with CFTR and AQP5 expression and localization during human airway epithelial cell differentiation. Experimental cell research 28 17553491
2016 AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study. Journal of translational medicine 25 27871297
2015 Spatial distributions of AQP5 and AQP0 in embryonic and postnatal mouse lens development. Experimental eye research 25 25595964
2007 Effect of cevimeline on radiation-induced salivary gland dysfunction and AQP5 in submandibular gland in mice. The Bulletin of Tokyo Dental College 25 17978545
2021 Unraveling Human AQP5-PIP Molecular Interaction and Effect on AQP5 Salivary Glands Localization in SS Patients. Cells 24 34440877
2010 Roles of lysosomal proteolytic systems in AQP5 degradation in the submandibular gland of rats following chorda tympani parasympathetic denervation. American journal of physiology. Gastrointestinal and liver physiology 24 20689061
2006 Regulation of MUC5AC mucin secretion by depletion of AQP5 in SPC-A1 cells. Biochemical and biophysical research communications 24 16500622
2018 Effect of AQP-5 silencing by siRNA interference on chemosensitivity of breast cancer cells. OncoTargets and therapy 23 29922074
2015 Hyperbaric oxygen therapy palliates lipopolysaccharide-induced acute lung injury in rats by upregulating AQP1 and AQP5 expression. Experimental lung research 23 26317897
2013 Hypoxia and hypoxia mimetics decrease aquaporin 5 (AQP5) expression through both hypoxia inducible factor-1α and proteasome-mediated pathways. PloS one 23 23469202
2011 Abnormal subcellular localization of AQP5 and downregulated AQP5 protein in parotid glands of streptozotocin-induced diabetic rats. Biochimica et biophysica acta 23 21295117
2024 Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in Sjogren's syndrome via lipid ROS/pSTAT4/AQP5 axis. Free radical biology & medicine 22 38574973
2021 AQP5 regulates vimentin expression via miR-124-3p.1 to protect lens transparency. Experimental eye research 22 33582182
2020 MiR-185-3p mimic promotes the chemosensitivity of CRC cells via AQP5. Cancer biology & therapy 22 32588739
2013 Down-regulated expression of AQP5 on lung in rat DIC model induced by LPS and its effect on the development of pulmonary edema. Pulmonary pharmacology & therapeutics 22 23538169
2008 Comparative expression analysis of aquaporin-5 (AQP5) in keratoconic and healthy corneas. Molecular vision 22 18449356
2008 Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor agonist. American journal of physiology. Gastrointestinal and liver physiology 22 18450949
2022 Helicobacter pylori infection activates Wnt/β-catenin pathway to promote the occurrence of gastritis by upregulating ASCL1 and AQP5. Cell death discovery 21 35538066
2020 AQP5 regulates the proliferation and differentiation of epidermal stem cells in skin aging. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 21 32965322
2015 Activation of muscarinic receptors in rat parotid acinar cells induces AQP5 trafficking to nuclei and apical plasma membrane. Biochimica et biophysica acta 21 25603543
2015 Effects of total glucosides of peony on AQP-5 and its mRNA expression in submandibular glands of NOD mice with Sjogren's syndrome. European review for medical and pharmacological sciences 21 25635992
2021 Lacrimal gland homeostasis is maintained by the AQP5 pathway by attenuating endoplasmic reticulum stress inflammation in the lacrimal gland of AQP5 knockout mice. Molecular vision 20 35002213
2014 miR-96 and miR-330 overexpressed and targeted AQP5 in lipopolysaccharide-induced rat lung damage of disseminated intravascular coagulation. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 20 24806323
2009 Apoptosis and expression of AQP5 and TGF-beta in the irradiated rat submandibular gland. Cancer research and treatment 20 19809564
2003 Expression of aquaporin 1 and 5 in the developing mouse inner ear and audiovestibular assessment of an Aqp5 null mutant. Journal of the Association for Research in Otolaryngology : JARO 20 12943377
2018 Downregulation of Aquaporins (AQP1 and AQP5) and Na,K-ATPase in Porcine Reproductive and Respiratory Syndrome Virus-Infected Pig Lungs. Inflammation 19 29532265
2018 LipoxinA4 attenuates acute pancreatitis-associated acute lung injury by regulating AQP-5 and MMP-9 expression, anti-apoptosis and PKC/SSeCKS-mediated F-actin activation. Molecular immunology 19 30219663
2017 Proteomic analysis reveals an impaired Ca2+/AQP5 pathway in the submandibular gland in hypertension. Scientific reports 19 29109472
2017 The Expression of AQP5 and UTs in the Sweat Glands of Uremic Patients. BioMed research international 19 29279852
2022 A novel and low-toxic peptide DR3penA alleviates pulmonary fibrosis by regulating the MAPK/miR-23b-5p/AQP5 signaling axis. Acta pharmaceutica Sinica. B 18 36873181
2021 AQP3 and AQP5-Potential Regulators of Redox Status in Breast Cancer. Molecules (Basel, Switzerland) 18 33947079
2020 Amelioration of airway inflammation and pulmonary edema by Teucrium stocksianum via attenuation of pro-inflammatory cytokines and up-regulation of AQP1 and AQP5. Respiratory physiology & neurobiology 18 33144273
2017 A mosquito entomoglyceroporin, Aedes aegypti AQP5, participates in water transport across the Malpighian tubules of larvae. The Journal of experimental biology 18 28760831
2019 Urinary AQP5 is independently associated with eGFR decline in patients with type 2 diabetes and nephropathy. Diabetes research and clinical practice 16 31377226
2016 S-allylmercapto-l-cysteine modulates MUC5AC and AQP5 secretions in a COPD model via NF-кB signaling pathway. International immunopharmacology 16 27517516
2014 Effect of P2X7 receptor knockout on AQP-5 expression of type I alveolar epithelial cells. PloS one 16 24941004
2012 DNA demethylating agent decitabine increases AQP5 expression and restores salivary function. Journal of dental research 16 22522773
2021 MicroRNA‑1271‑5p alleviates the malignant development of hepatitis B virus‑mediated liver cancer via binding to AQP5. Molecular medicine reports 15 33760167
2016 Urine AQP5 is a potential novel biomarker of diabetic nephropathy. Journal of diabetes and its complications 15 27103565
2015 AQP1, AQP5, Bcl-2 and p16 in pharyngeal squamous cell carcinoma. The Journal of laryngology and otology 15 26074259
2022 Apigenin, a Single Active Component of Herbal Extract, Alleviates Xerostomia via ERα-Mediated Upregulation of AQP5 Activation. Frontiers in pharmacology 14 35264956
2019 Ovatodiolide suppresses inflammatory response in BEAS-2B cells by regulating the CREB/AQP5 pathway, and sensitizes nasopharyngeal carcinoma cells to radiation therapy. European journal of pharmacology 14 31323224
2012 Unilateral maxillary molar extraction influences AQP5 expression and distribution in the rat submandibular salivary gland. Archives of oral biology 14 22424887
2020 Maladjustment of β-CGRP/α-CGRP Regulation of AQP5 Promotes Transition of Alveolar Epithelial Cell Apoptosis to Pulmonary Fibrosis. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 13 32746702
2019 Potential forensic application of receptor for advanced glycation end products (RAGE) and aquaporin 5 (AQP5) as novel biomarkers for diagnosis of drowning. Journal of forensic and legal medicine 13 30677703
2009 Trafficking of GFP-AQP5 chimeric proteins conferred with unphosphorylated amino acids at their PKA-target motif ((152)SRRTS) in MDCK-II cells. The journal of medical investigation : JMI 13 19262015
2016 Overexpression of AQP5 Was Detected in Axillary Sweat Glands of Primary Focal Hyperhidrosis Patients. Dermatology (Basel, Switzerland) 12 26930592
2006 Aquaporins in chicken: localization of ck-AQP5 along the small and large intestine. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 12 16418008

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