Affinage

AQP5

Aquaporin-5 · UniProt P55064

Length
265 aa
Mass
28.3 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AQP5 is a regulated water and CO2-selective gas channel expressed at apical membranes of secretory and barrier epithelia, where it mediates transcellular water transport and participates in cell volume sensing (PMID:9755069, PMID:19273840). Its trafficking from intracellular vesicles to the apical plasma membrane requires microtubule-dependent transport and is triggered by intracellular Ca²⁺ signaling downstream of muscarinic M3 receptors; this process involves lipid raft dissociation, caveolin-1-dependent TRPC1 Ca²⁺ influx, and regulation by PKA phosphorylation at Ser156 and by the interacting partner PIP, while AQP5 also partners with TRPV4 via its N-terminus to enable hypotonic regulatory volume decrease (PMID:10600522, PMID:16107506, PMID:23203809, PMID:16571723, PMID:34440877). Transcription of AQP5 is activated by a GATA6/Sp1/p300 histone acetylation axis, repressed by Dot1a-mediated H3K79 methylation, suppressed under hypoxia through HIF-1α, downregulated by LPS-induced NF-κB/AP-1 complexes, and inhibited by lipid ROS-driven pSTAT4 promoter binding in Sjögren's syndrome (PMID:28615712, PMID:23326416, PMID:23469202, PMID:20522648, PMID:38574973). Missense mutations in AQP5 cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma, and in cancer contexts AQP5 promotes invasion and stemness through phospho-Ser156-dependent c-Src interaction, NF-κB-driven EMT, and TRIM21-mediated K63-ubiquitination of ULK1 to activate autophagy (PMID:23830519, PMID:18478076, PMID:28619511, PMID:36372898).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Establishing where AQP5 acts: immunolocalization resolved AQP5 to apical membranes of corneal, lacrimal, salivary, and type I lung epithelial cells, defining it as an apical water channel of diverse secretory epithelia.

    Evidence Immunohistochemistry and immunoelectron microscopy with affinity-purified antibody across multiple tissues

    PMID:9755069

    Open questions at the time
    • No functional water permeability measurement in these tissues at this stage
    • Mechanism of apical targeting unknown
  2. 1999 High

    Defining the trafficking mechanism: Ca²⁺ elevation was shown to drive AQP5 translocation to the plasma membrane via a microtubule-dependent, microfilament-independent route, establishing regulated vesicular insertion as the basis for AQP5 surface delivery.

    Evidence Confocal microscopy of AQP5-transfected HSG cells with thapsigargin/ionophore stimulation and pharmacological cytoskeletal disruption

    PMID:10022971 PMID:10600522

    Open questions at the time
    • Identity of motor proteins and vesicle carriers unknown
    • Whether Ca²⁺ acts directly on vesicle fusion or via an intermediate kinase unclear
  3. 2005 High

    Resolving the receptor-to-membrane pathway: M3 muscarinic receptor activation and PKA signaling were shown to control AQP5 apical insertion, with lipid raft association/dissociation serving as a membrane-organizing step during trafficking.

    Evidence Detergent solubility/flotation assays and immunoEM in parotid gland (M3 agonist cevimeline); PKA inhibitor H-89 in duodenal Brunner's gland VIP-stimulated slices

    PMID:15650134 PMID:16107506

    Open questions at the time
    • Whether PKA phosphorylates AQP5 directly versus raft components not resolved
    • PKA site identity not yet mapped
  4. 2006 High

    Linking AQP5 to volume sensing: AQP5 was shown to physically associate with TRPV4 via its N-terminus at the apical membrane, and both AQP5-null and TRPV4-null cells lost Ca²⁺ entry and regulatory volume decrease upon hypotonicity, establishing AQP5 as a co-sensor for osmotic stress rather than a passive pore.

    Evidence Co-immunoprecipitation, AQP5/TRPV4 knockout acinar cells, N-terminal deletion mutant, Ca²⁺ imaging, and cell volume assays

    PMID:16571723

    Open questions at the time
    • Structural basis of N-terminus–TRPV4 interaction unresolved
    • Whether AQP5–TRPV4 coupling operates in non-salivary tissues unknown
  5. 2007 High

    Dissecting the PKA phosphorylation site: Ser156 was confirmed as the PKA substrate but S156A did not block membrane targeting, while the NPA-motif mutant N185D retained AQP5 in the cytoplasm, separating channel maturation/folding requirements from kinase-dependent regulation.

    Evidence Site-directed mutagenesis (S156A, N185D) in stably transfected BEAS-2B cells on permeable support with cAMP/PKA pharmacological manipulation

    PMID:18042467

    Open questions at the time
    • What downstream process Ser156 phosphorylation controls if not trafficking
    • Whether N185D causes global misfolding versus specific NPA-dependent retention
  6. 2008 Medium

    Establishing an oncogenic signaling role: phospho-Ser156 was required for AQP5 to interact with activated c-Src and promote cell invasion, proliferation, and EMT, revealing a non-channel, signaling-scaffold function.

    Evidence Invasion assays, SH3-domain protein array, co-IP with phospho-Src in BEAS-2B/NIH3T3; overexpression/siRNA in K562 CML cells

    PMID:18423983 PMID:18478076 PMID:18612408

    Open questions at the time
    • Whether AQP5–c-Src interaction requires water channel activity unknown
    • Generalizability of CML BCR-ABL1 connection not independently replicated
  7. 2009 High

    Expanding substrate selectivity: functional reconstitution in oocytes demonstrated AQP5 conducts CO₂ with high selectivity over NH₃, extending its physiological role beyond water to gas transport.

    Evidence Xenopus oocyte expression with surface pH measurement and osmotic water permeability comparison to AQP1/AQP4

    PMID:19273840

    Open questions at the time
    • Physiological relevance of CO₂ transport via AQP5 in vivo not established
    • Molecular determinants of CO₂ vs. NH₃ selectivity not mapped
  8. 2010 High

    Defining transcriptional repression: LPS was shown to downregulate AQP5 transcription via a physical NF-κB(p65)/p-c-Jun/c-Fos complex binding the AQP5 promoter, and parasympathetic denervation was shown to degrade AQP5 protein through lysosomal/autophagic pathways involving cathepsins B and L.

    Evidence TLR4-mutant mice, EMSA/co-IP on AQP5 promoter; chorda tympani denervation with lysosomal co-localization and protease inhibitor rescue

    PMID:20522648 PMID:20689061

    Open questions at the time
    • Whether NF-κB directly binds DNA or acts through AP-1 composite elements not fully resolved
    • Whether autophagy-mediated AQP5 degradation is a general regulatory mechanism beyond denervation
  9. 2012 High

    Identifying the Ca²⁺ entry gateway: caveolin-1 was required for agonist-induced AQP5 apical translocation because it enables TRPC1-mediated Ca²⁺ influx; Cav1 knockout ablated the response and adenoviral rescue restored it.

    Evidence Cav1 knockout mice, adenoviral Cav1 re-expression, Ca²⁺ imaging, surface biotinylation, fluid secretion measurement in salivary glands

    PMID:23203809

    Open questions at the time
    • Whether Cav1 scaffolds AQP5 vesicles directly or acts solely through TRPC1-Ca²⁺ unclear
    • Role of other TRP channels not excluded
  10. 2013 High

    Resolving chromatin-level control and a disease link: Dot1a-mediated H3K79 methylation was shown to repress AQP5 transcription (with derepression causing AQP5–AQP2 hetero-interaction that impairs AQP2 surface expression in kidney), and missense AQP5 mutations were identified as the cause of autosomal-dominant palmoplantar keratoderma.

    Evidence ChIP for H3K79me at AQP5 promoter, co-IP of AQP5–AQP2, surface biotinylation in Dot1l-deficient cells; exome sequencing of keratoderma families with immunofluorescence of patient skin

    PMID:23326416 PMID:23830519

    Open questions at the time
    • Whether AQP5–AQP2 interaction is physiological or only pathological upon AQP5 overexpression
    • Functional channel assay for keratoderma mutants not performed
  11. 2017 High

    Building the epigenetic activation model and identifying tissue-specific channel function: GATA6/Sp1/p300 were shown to activate AQP5 via H3 acetylation opposed by HDAC3, and AQP5 was demonstrated to form functional water channels in lens fiber cells with species-specific membrane insertion.

    Evidence ChIP for H3 acetylation, co-IP of GATA6/Sp1/p300/HDAC3, luciferase reporter in salivary cells; fluorescence dye dilution water permeability assay with HgCl₂ inhibition in mouse and rat lens

    PMID:28615712 PMID:29118028

    Open questions at the time
    • Signals that switch HDAC3 occupancy at the AQP5 promoter unidentified
    • Whether GATA6/Sp1 axis operates in non-salivary AQP5-expressing tissues unknown
  12. 2021 High

    Identifying PIP as an apical-targeting partner and AQP5's role in lens clarity via miR-124-3p.1: PIP was shown to interact with the AQP5 C-terminus to regulate apical localization in salivary glands (with altered distribution in Sjögren's syndrome), and AQP5 knockout in lens caused opacity through miR-124-3p.1 downregulation and vimentin upregulation.

    Evidence Reciprocal co-IP, PIP knockout mice, domain mapping; CRISPR AQP5 KO mice, dual luciferase reporter for miR-124-3p.1–vimentin, agomir rescue in organ culture

    PMID:33582182 PMID:34440877

    Open questions at the time
    • Mechanism by which AQP5 regulates miR-124-3p.1 expression entirely unknown
    • PIP–AQP5 structural interface not resolved at atomic level
  13. 2022 Medium

    Revealing a non-channel autophagy-scaffold function in cancer: AQP5 was shown to recruit E3 ligase TRIM21 to ULK1, inducing K63-ubiquitination that activates autophagy and sustains gastric cancer stemness.

    Evidence Co-IP/mass spectrometry, ubiquitination assay, sphere formation and tumorigenesis assays in gastric cancer stem cells

    PMID:36372898

    Open questions at the time
    • Whether AQP5–TRIM21–ULK1 axis operates in non-cancer contexts unknown
    • Domain on AQP5 mediating TRIM21 recruitment not mapped
    • Single-lab finding awaits independent replication
  14. 2024 High

    Connecting lipid peroxidation to AQP5 silencing in Sjögren's syndrome: GPX4 deficiency was shown to cause lipid ROS accumulation that activates STAT4 phosphorylation, and pSTAT4 directly binds and represses the AQP5 promoter, reducing salivary secretion.

    Evidence ChIP confirming pSTAT4 at AQP5 promoter; GPX4 OE/KD, ferrostatin-1 rescue in SGECs and SS mouse model

    PMID:38574973

    Open questions at the time
    • Whether pSTAT4-mediated AQP5 repression operates outside Sjögren's disease context
    • Whether other aquaporins are similarly regulated by this lipid ROS–STAT4 axis

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of AQP5's non-channel scaffolding interactions (c-Src, TRPV4, TRIM21), whether CO₂ transport by AQP5 is physiologically significant in vivo, and how the multiple transcriptional inputs (GATA6/Sp1, Dot1a, NF-κB, HIF-1α, pSTAT4) are integrated in different tissues.
  • No high-resolution structure of AQP5 in complex with any signaling partner
  • In vivo relevance of CO₂ selectivity not tested
  • No systems-level model integrating the diverse transcriptional and post-translational regulatory inputs

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 9 GO:0031410 cytoplasmic vesicle 3 GO:0005634 nucleus 1
Pathway
R-HSA-9609507 Protein localization 7 R-HSA-162582 Signal Transduction 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-382551 Transport of small molecules 4 R-HSA-4839726 Chromatin organization 2 R-HSA-9612973 Autophagy 2
Partners
AQP2CAV1PIPSRCTRIM21TRPV4ULK1

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 AQP5 protein is selectively localized to the apical membrane of corneal epithelial surface cells, apical membranes of acinar cells in lacrimal gland, microvilli of serous salivary gland intracellular secretory canaliculi, and apical membranes of type I pulmonary epithelial cells, consistent with a role in water transport at these sites. Immunohistochemistry and immunoelectron microscopy with affinity-purified anti-AQP5 antibody; RNase protection assay The American journal of physiology High 9755069
1999 AQP5 in salivary gland acinar cells is restricted to apical membranes including intercellular secretory canaliculi; upon isoproterenol (β-adrenergic) stimulation, apical AQP5 staining in parotid acinar cells shifts to a clustered dot pattern, suggesting stimulus-dependent redistribution. Immunofluorescence microscopy; anti-AQP5 antibody raised and validated Cell and tissue research Medium 10022971
1999 AQP5 trafficking to the plasma membrane in salivary gland cells is triggered by an increase in intracellular Ca2+ (induced by thapsigargin or calcium ionophore A-23187), and requires intact microtubules but not microfilaments, implicating vesicle-cytoskeleton interaction in AQP5 membrane targeting. Confocal laser microscopy of AQP5-transfected HSG cells; pharmacologic inhibition with colchicine/vinblastine (microtubule inhibitors) and cytochalasin B (microfilament inhibitor) Biochemical and biophysical research communications High 10600522
2005 AQP5 localizes in intracellular lipid rafts in rat parotid interlobular duct cells; activation of M3 muscarinic acetylcholine receptors (mAChR) by cevimeline induces AQP5 trafficking to the apical plasma membrane via intracellular Ca2+ signaling, followed by AQP5 dissociation from lipid rafts to non-raft domains on the apical membrane. Immunofluorescence/immunoelectron microscopy; detergent solubility assay (Triton X-100); sucrose density gradient flotation; calcium ionophore A-23187 mimicry; co-localization with lipid raft markers flotillin-2 and GM1 American journal of physiology. Cell physiology High 16107506
2005 In rat duodenal Brunner's gland cells, VIP induces AQP5 translocation from secretory granule membranes to the apical membrane in a PKA-dependent (blocked by H-89) but PKC-independent manner, without affecting AQP1 localization. Immunohistochemistry; in vitro duodenal slice assay with VIP; protein kinase inhibitors H-7, H-89, calphostin C; in vivo VIP injection American journal of physiology. Gastrointestinal and liver physiology High 15650134
2006 AQP5 associates with TRPV4 at the apical membrane of salivary gland acinar cells; the N-terminus of AQP5 is required for TRPV4 activation by hypotonicity (N-terminus-deleted AQP5 suppresses TRPV4 activation); hypotonicity increases co-association and surface expression of AQP5 and TRPV4; both AQP5-null and TRPV4-null acinar cells show greatly reduced Ca2+ entry and loss of regulatory volume decrease (RVD) in response to hypotonicity; actin depolymerization reduces AQP5-TRPV4 co-association and RVD. Co-immunoprecipitation; AQP5 knockout and TRPV4 knockout mouse acinar cells; N-terminus deletion mutant expression; Ca2+ imaging; cell volume measurements; pharmacological TRPV4 activation/inhibition The Journal of biological chemistry High 16571723
2007 In bronchial epithelial cells, AQP5 Ser156 is phosphorylated by PKA (abolished in S156A mutant); the N185D mutation (disrupting second NPA motif) retains AQP5 in the cytoplasm rather than the apical membrane, whereas S156A does not affect membrane expression, indicating that membrane targeting of AQP5 involves the NPA motif but PKA phosphorylation at Ser156 is not required for apical membrane expression. Stable transfection in BEAS-2B cells on permeable support; immunofluorescence; site-directed mutagenesis (S156A, N185D); cAMP/PKA pharmacological manipulation (H89, cpt-cAMP) Biochemical and biophysical research communications High 18042467
2008 AQP5 promotes cell invasion and epithelial-to-mesenchymal transition (EMT) in lung cells through phosphorylation at Ser156 and subsequent interaction with activated c-Src (phospho-Tyr416); membrane trafficking mutant N185D and phosphorylation-blocking mutant S156A both abolish invasion and c-Src interaction. In vitro invasion assay; stable transfection in BEAS-2B and NIH3T3 cells; SH3-domain protein array; co-immunoprecipitation with activated c-Src; site-directed mutagenesis (N185D, S156A) PloS one High 18478076
2008 AQP5 overexpression in CML cells (K562) increases BCR-ABL1 phosphorylation and cell proliferation; siRNA-mediated AQP5 knockdown reduces proliferation, decreases BCR-ABL1 phosphorylation, and increases caspase-9 activity, indicating AQP5 promotes survival/proliferation and suppresses apoptosis in CML cells. siRNA knockdown; AQP5 overexpression; immunoblotting; flow cytometry; cell proliferation assay PloS one Medium 18612408
2008 AQP5 overexpression induces cell proliferation and oncogenic transformation dependent on cAMP-PKA phosphorylation of a cytoplasmic loop consensus site (Ser156); preferential phosphorylation of this site is found in tumor samples. Ectopic AQP5 expression in vitro and in vivo xenograft; PKA phosphorylation site mutagenesis; immunoblotting of tumor vs. normal samples Cancer letters Medium 18423983
2009 AQP5 expressed in Xenopus oocytes confers selective CO2 permeability (increased surface pH change and faster time constants with CO2 exposure) compared with water-injected controls, but does not conduct NH3, establishing AQP5 as a CO2-selective gas channel with higher CO2/NH3 selectivity than AQP1 or AQP4. Xenopus oocyte expression system; surface pH measurement assay; osmotic water permeability (Pf) measurement; comparison with AQP1, AQP4, AmtB, RhAG Proceedings of the National Academy of Sciences of the United States of America High 19273840
2009 In rat parotid gland, AQP5 dephosphorylation at the PKA consensus motif 152SRRTS promotes translocation to the apical membrane; microtubules but not microfilaments are required for this trafficking event. GFP-AQP5 chimeric protein expression in MDCK-II cells; PKA inhibitor H-89; site-directed mutagenesis of Ser152; colchicine/cytochalasin B treatment; confocal microscopy The journal of medical investigation Medium 19262015
2010 LPS-induced downregulation of AQP5 mRNA in parotid gland is mediated through a transcription factor complex of NF-κB (p65), p-c-Jun, and c-Fos acting on NF-κB-responsive elements in the AQP5 promoter; this is blocked by inhibitors of IκB kinase, 26S proteasome, ERK1/2, JNK, and p38 MAPK; co-immunoprecipitation revealed physical association of NF-κB, p-c-Jun, and c-Fos. In vivo LPS injection in C3H/HeN and TLR4-mutant C3H/HeJ mice; tissue culture with kinase inhibitors; co-immunoprecipitation; EMSA/protein-binding assay on AQP5 promoter sequences The American journal of pathology High 20522648
2010 Parasympathetic denervation (chorda tympani) decreases AQP5 protein in submandibular gland via lysosomal degradation (enhanced by autophagosomes/lysosomes, reversed by chloroquine); cathepsins B and L are implicated as degrading enzymes; M3 mAChR agonist cevimeline recovers AQP5 protein levels post-denervation. Chorda tympani denervation in rat; autophagosome marker LC3B-II western blot; TUNEL apoptosis assay; lysosomal fraction in vitro degradation assay; protease inhibitor experiments; immunohistochemistry for AQP5/Lamp2/LC3B co-localization American journal of physiology. Gastrointestinal and liver physiology High 20689061
2012 Caveolin-1 is required for agonist-stimulated AQP5 translocation to the apical membrane of salivary gland acinar cells; in Cav1-/- mice, AQP5 apical localization is disrupted and agonist-induced surface expression of AQP5 (which requires Ca2+ influx via TRPC1 channels) is abrogated; adenoviral re-expression of Cav1 restores AQP5 apical targeting and fluid secretion. Cav1 knockout mice; adenoviral Cav1 re-expression; Ca2+ imaging; immunofluorescence for AQP5 apical localization; surface biotinylation assay; fluid secretion measurement Journal of cell science High 23203809
2013 AQP5 is a transcriptional target repressed by histone H3K79 methyltransferase Dot1a; in Dot1l-deficient kidney cells, AQP5 is upregulated and colocalizes with AQP2; AQP5 directly interacts with AQP2 (co-immunoprecipitation) and impairs AQP2 surface localization, with the AQP5/AQP2 complex partially residing in the ER/Golgi. cDNA array; real-time RT-qPCR; luciferase reporter assay; cell surface biotinylation; co-immunoprecipitation; co-localization microscopy; ChIP showing Dot1a/H3diMe-K79 occupancy at AQP5 promoter PloS one High 23326416
2013 Missense mutations in AQP5 cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma; protein structure analysis suggests these variants affect normal channel regulation; immunofluorescence shows mutant AQP5 is trafficked normally to the plasma membrane in stratum granulosum, suggesting the mutations likely produce open/dysregulated channels rather than trafficking defects. Exome sequencing; protein structure analysis; immunofluorescence of patient skin biopsies American journal of human genetics Medium 23830519
2013 Hypoxia and hypoxia mimetic cobalt decrease AQP5 expression (~70%) in mouse lung; HIF-1α is a key mediator (dominant-negative HIF-1α and siRNA block the effect); proteasome inhibitors abolish both hypoxia-induced and cobalt-induced AQP5 decrease at both protein and mRNA levels, indicating the proteasome pathway stabilizes HIF-1α and/or unidentified transcription factors that regulate AQP5 transcription. Mouse hypoxia exposure; MLE-12 cell line; cobalt treatment; HIF-1α dominant-negative mutants and siRNA; proteasome inhibitors lactacystin and PI-III; hnRNA quantification by real-time PCR PloS one High 23469202
2015 Activation of muscarinic receptors in rat parotid acinar cells induces AQP5 translocation to the nucleus, apical plasma membrane, and lateral plasma membrane; AQP5 presence in the nuclear membrane coincides with nuclear shrinkage, suggesting AQP5 facilitates water transport across the nuclear membrane. Immunoconfocal and immunoelectron microscopy; western blot of nuclear fractions; detergent solubility and sucrose density flotation; atropine (mAChR antagonist) pretreatment Biochimica et biophysica acta Medium 25603543
2017 AQP5 forms functional water channels in rodent lens fiber cells; AQP5 membrane insertion in cortical fiber cells modulates water permeability (PH2O); species-specific differences in AQP5 subcellular distribution (membranous in mouse, cytoplasmic in rat) correlate with Hg2+-sensitive PH2O contributions; organ culture promotes AQP5 membrane insertion in rat lens cortical fiber cells with corresponding increase in Hg2+-sensitive PH2O. Fluorescence dye dilution assay for PH2O; HgCl2 inhibition; immunolabeling of lens sections and fiber membrane vesicles; organ culture American journal of physiology. Cell physiology High 29118028
2017 GATA6 and Sp1 activate AQP5 transcription via histone H3 acetylation; HDAC3 represses AQP5 by binding Sp1 and reducing H3 acetylation at the AQP5 promoter; p300 histone acetyltransferase cooperates with GATA6/Sp1 to activate AQP5; HDAC inhibitor SAHA increases AQP5 expression and H3 acetylation at the Aqp5 promoter. HDAC3 overexpression/knockdown; GATA6/p300 knockdown/overexpression; luciferase reporter assay; ChIP for H3/H4 acetylation; co-immunoprecipitation of GATA6/Sp1/p300/HDAC3 interactions; SAHA treatment Scientific reports High 28615712
2017 In hyperosmolarity-treated human corneal epithelial cells, AQP5 upregulation mediates JNK1/2 MAPK activation, proinflammatory cytokine expression (IL-1β, IL-6, IL-8, TNF-α, caspase-1), and cell death; siRNA knockdown of AQP5 or JNK1/2 inhibition with SP600125 reduces these effects, placing AQP5 upstream of JNK1/2 signaling in hyperosmotic corneal injury. siRNA AQP5 gene silencing; SP600125 JNK1/2 inhibitor; real-time RT-PCR; western blot for AQP5 and p-JNK1/2; TUNEL assay; step increases in osmolarity up to 550 mOsm Scientific reports Medium 28680052
2017 AQP5 downregulation in HCC cells suppresses EMT and tumor metastasis partly via inactivation of the NF-κB signaling pathway, altering expression of E-cadherin, α-catenin, N-cadherin, and vimentin. AQP5 knockdown in HCC cell lines; in vitro invasion assay; in vivo metastasis model; western blot for EMT markers and NF-κB pathway components Biochemical and biophysical research communications Medium 28619511
2021 Prolactin-inducible protein (PIP) physically interacts with AQP5 via the AQP5 C-terminus (one PIP molecule per AQP5 tetramer); PIP knockout in mice and PIP misexpression in Sjögren's syndrome patients correlate with altered AQP5 distribution at the acinar apical membrane, indicating PIP regulates AQP5 localization in salivary glands. Co-immunoprecipitation in vitro and in vivo (mouse and human salivary glands); PIP knockout mice; structural binding analysis (C-terminus deletion); immunofluorescence of human minor salivary glands from SS patients Cells High 34440877
2021 AQP5 knockout in mouse lens leads to mild lens opacity at ~6 months; mechanistically, AQP5 loss downregulates miR-124-3p.1, which normally suppresses vimentin (a dual luciferase reporter confirmed vimentin as direct miR-124-3p.1 target); AQP5 knockout and AQP5-L51P mutation increase vimentin expression, contributing to lens opacity; miR-124-3p.1 agomir reduces lens opacity and vimentin in both WT and KO mice. CRISPR/Cas9 AQP5 knockout mice; whole exome sequencing; dual luciferase reporter assay; qRT-PCR; western blot; immunofluorescence; miR-124-3p.1 agomir organ culture Experimental eye research High 33582182
2024 In Sjögren's syndrome salivary gland epithelial cells, reduced GPX4 expression leads to lipid ROS accumulation, which activates STAT4 phosphorylation and nuclear translocation; nuclear pSTAT4 binds the AQP5 promoter (confirmed by ChIP) and inhibits AQP5 transcription, reducing salivary secretion; GPX4 overexpression reverses this and restores AQP5 expression. GPX4 overexpression/knockdown in SGECs; ChIP assay confirming pSTAT4 binding at AQP5 promoter; lipid ROS inhibitor ferrostatin-1 in vitro and in vivo; SS mouse model; immunohistochemistry; western blot; bioinformatics of SS patient GSE databases Free radical biology & medicine High 38574973
2022 AQP5 recruits E3 ubiquitin ligase TRIM21 to the key autophagy protein ULK1, inducing K63-mediated ubiquitination of ULK1 and activating autophagy (LC3I/LC3II conversion) in gastric cancer stem cells; this autophagy activation is required for AQP5-driven cancer stem cell biological functions. Transcriptome sequencing; proteomic detection; mass spectrometry; co-immunoprecipitation; ubiquitination assay; sphere formation and tumorigenesis assays Journal of experimental & clinical cancer research Medium 36372898

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 207 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 193 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 136 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 109 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
2008 Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML). PloS one 57 18612408
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 55 22226856
2020 Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions. International journal of molecular sciences 53 32053992
2013 Aqp5 is a new transcriptional target of Dot1a and a regulator of Aqp2. PloS one 53 23326416
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
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
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 48 24752576
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 46 31922312
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
2023 NNMT enriches for AQP5+ cancer stem cells to drive malignant progression in early gastric cardia adenocarcinoma. Gut 44 36977555
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
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
2017 AQP5 promotes hepatocellular carcinoma metastasis via NF-κB-regulated epithelial-mesenchymal transition. Biochemical and biophysical research communications 36 28619511
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
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
2009 Correlation between salivary secretion and salivary AQP5 levels in health and disease. The journal of medical investigation : JMI 30 20224222
1997 Closely spaced tandem arrangement of AQP2, AQP5, and AQP6 genes in a 27-kilobase segment at chromosome locus 12q13. Genomics 30 9268644
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
2017 Cell-specific expression of aquaporin-5 (Aqp5) in alveolar epithelium is directed by GATA6/Sp1 via histone acetylation. Scientific reports 27 28615712
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
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
2021 AQP5 regulates vimentin expression via miR-124-3p.1 to protect lens transparency. Experimental eye research 21 33582182
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 20 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 20 25635992
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
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 19 38574973
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 19 35002213
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
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
2017 The Expression of AQP5 and UTs in the Sweat Glands of Uremic Patients. BioMed research international 18 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 17 36873181
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
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
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 13 31323224
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