Affinage

KLK8

Kallikrein-8 · UniProt O60259

Length
260 aa
Mass
28.0 kDa
Annotated
2026-06-10
62 papers in source corpus 19 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLK8 (neuropsin) is a secreted, Ca2+-stimulated and Zn2+-inhibited trypsin-like serine protease whose activity is governed by an allosteric surface-loop network that couples its two antagonistic cation-binding sites to substrate selectivity (PMID:30013126). In the hippocampus, extracellular KLK8 shapes synaptic plasticity and circuit remodeling: it is required for late synaptic tagging and cross-tagging between LTP and LTD through integrin β1/CaMKII and L-type voltage-dependent Ca2+ channel signaling (PMID:18216192, PMID:21646406), supports neurite outgrowth and fasciculation (PMID:11880192), and sustains dendritic architecture, spine density, and memory consolidation via PKA–CREB signaling (PMID:29967374). A key neural substrate is the extracellular domain of NCAM1, whose KLK8-mediated cleavage drives neuronal apoptosis and is engaged in a chronic-stress depression model (PMID:37076499). Across peripheral tissues, KLK8 acts through proteolytic activation of receptor and matrix substrates: it cleaves pro-HGF to trigger Met/Src/Btk/NF-κB signaling and microglial neuroinflammation (PMID:40521191), and it activates protease-activated receptor PAR1 — while disarming rather than activating human PAR1/PAR2 in some contexts — to promote epithelial–mesenchymal transition in colorectal cancer and myocardial fibrosis via TGF-β1/Smad3 (PMID:22505524, PMID:34552064, PMID:39578836). KLK8 also participates in epidermal terminal differentiation and cell-envelope assembly (PMID:14616360). A human-specific intronic mutation generates a brain-restricted type II splice form of neuropsin found only in humans (PMID:17487847).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2002 Medium

    Established that extracellular KLK8 protease activity has direct morphogenic effects on neurons and links to epidermal differentiation, framing it as a tissue-remodeling protease rather than a passive secretory product.

    Evidence Recombinant neuropsin application to hippocampal neuron cultures with morphological readout; Northern/in situ analysis of human skin and calcium-induced keratinocyte differentiation

    PMID:11880192 PMID:12147714

    Open questions at the time
    • No substrate identified for the neurite-outgrowth or epidermal effects
    • Skin data are correlative mRNA expression without loss-of-function
  2. 2003 Medium

    Genetic loss-of-function established that KLK8 contributes to early epidermal differentiation and cell-envelope assembly, and revealed expression in immune (mast) cells.

    Evidence KLK8 knockout mice with UV-B injury and involucrin staining; mast cell cDNA/IHC during helminth infection

    PMID:12646205 PMID:14616360

    Open questions at the time
    • Mast cell expression has no established functional consequence
    • Direct epidermal substrate not defined
  3. 2008 High

    Resolved whether KLK8 has a defined role in synaptic plasticity by showing it is specifically required for tetanus-evoked late synaptic associativity converging on integrin/actin and LVDCC pathways.

    Evidence LTP recording in hippocampal slices from KLK8 knockout mice with pharmacological pathway dissection

    PMID:18216192

    Open questions at the time
    • Molecular substrate cleaved during tagging not identified
    • Link between protease activity and integrin/LVDCC signaling unresolved
  4. 2007 Medium

    Defined the molecular basis of a human-specific neuropsin isoform, showing a single intronic mutation is sufficient to create a brain-restricted type II splice form.

    Evidence Comparative primate sequencing, in vitro splicing assay, mutation-sufficiency test

    PMID:17487847

    Open questions at the time
    • Functional consequence of the type II isoform not established
    • Activity difference between isoforms unknown
  5. 2011 High

    Extended the plasticity role by showing KLK8 mediates synaptic cross-tagging between LTP and LTD via integrin β1 and CaMKII.

    Evidence LTP/LTD recording in hippocampal slices from KLK8 knockout mice with integrin β1 and CaMKII inhibition

    PMID:21646406

    Open questions at the time
    • Proteolytic substrate underlying cross-tagging not identified
  6. 2012 Medium

    Clarified KLK8 receptor specificity, showing it disarms human PAR1 and signals via rat but not human PAR2, distinguishing it from KLK14.

    Evidence Calcium, MAPK, β-arrestin and internalization assays plus synthetic PAR-peptide cleavage in PAR-expressing cells

    PMID:22505524

    Open questions at the time
    • Species-specific receptor behavior complicates extrapolation to human tissue
    • Single lab without reciprocal validation
  7. 2018 High

    Provided the structural and biochemical foundation, defining KLK8 subsite specificity and the dual allosteric regulation of activity by Ca2+ (stimulatory) and Zn2+ (inhibitory).

    Evidence X-ray crystallography (ligand-free and leupeptin-bound), positional scanning and PICS substrate profiling, kinetics, D70K/H99A mutagenesis, docking/MD

    PMID:30013126

    Open questions at the time
    • Physiological substrates cleaved in vivo not enumerated by structure alone
    • In vivo relevance of Ca2+/Zn2+ switch untested
  8. 2018 Medium

    Connected KLK8 to memory at the molecular level, showing it maintains dendritic morphology and PKA–CREB-dependent memory gene expression.

    Evidence siRNA and antisense knockdown in primary neurons and in vivo, dendritic/spine morphometry, Western blot for MAP2c/PKA/pCREB, behavioral tests

    PMID:29967374

    Open questions at the time
    • Substrate linking KLK8 to PKA/CREB not defined
    • Direct vs indirect effect on signaling unresolved
  9. 2021 Medium

    Identified PAR1 as the operative receptor for KLK8 in cancer progression and demonstrated a contributory role in Alzheimer-type pathology.

    Evidence KLK8 gain/loss-of-function in colorectal cancer with PAR1/PAR2 antagonists and xenografts; genetic Klk8 reduction in TgCRND8 mice with amyloid/tau and APP-processing readouts

    PMID:33341972 PMID:34552064

    Open questions at the time
    • Direct cleavage event upstream of PAR1 activation not shown in CRC
    • Mechanism linking KLK8 to APP processing not biochemically defined
  10. 2023 High

    Identified NCAM1 extracellular domain as a direct KLK8 substrate placing proteolysis upstream of neuronal apoptosis in depression.

    Evidence Adenoviral overexpression/knockdown in neurons and HT22 cells, cleavage assay, NCAM1 rescue (overexpression and mimetic peptide), CUMS model

    PMID:37076499

    Open questions at the time
    • Cleavage site and fragment fate not mapped
    • Relationship to the synaptic-tagging substrate unclear
  11. 2024 Medium

    Defined KLK8 as both a transcriptional target of SREBP1 and a driver of fibrosis/immune escape, broadening it into metabolic and immunomodulatory programs.

    Evidence EMSA for SREBF1/KLK8 promoter, Treg chemotaxis and CCL22 readouts in oral cancer; KLK8/PAR1 in cardiac fibroblasts with TGF-β1/Smad3 and DCM model

    PMID:39578836 PMID:39616730

    Open questions at the time
    • Direct substrate driving CCL22 secretion not identified
    • PAR1 cleavage by KLK8 in cardiac context inferred pharmacologically
  12. 2025 Medium

    Established KLK8 substrate cleavage events in vascular and inflammatory disease: pro-HGF activation driving Met/Src/Btk/NF-κB neuroinflammation, fibronectin/FAK inactivation in endothelial senescence, and SDC4 cleavage disrupting endothelial glycocalyx.

    Evidence Adenoviral overexpression, Co-IP/MS, pro-HGF cleavage assay and Met inhibition in microglia; KLK8 KO/overexpression in lung endothelium with FAK analysis; endothelial-specific Klk8 KO with SDC4 cleavage and LIFR pathway in diabetic nephropathy (one preprint)

    PMID:40521191 PMID:41310943

    Open questions at the time
    • CD44 interaction identified by Co-IP/MS not functionally validated
    • SDC4/LIFR findings remain in preprint form

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the structurally defined Ca2+/Zn2+ allosteric switch selects among the diverse documented substrates (NCAM1, pro-HGF, SDC4, fibronectin, PAR receptors) in different tissue microenvironments remains unresolved.
  • No unified substrate-selection model across tissues
  • Endogenous activation/inhibition of KLK8 in each context undefined
  • Direct cleavage sites for most non-NCAM1/pro-HGF substrates unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 1
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2
Partners
CD44F2RFN1HGFIKBANCAM1PAR1SDC4

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Crystal structures of KLK8 with a ligand-free active site and with the inhibitor leupeptin were determined, revealing subsite specificity and Ca2+ bound to the 75-loop. Substrate profiling using positional scanning with fluorogenic tetrapeptides and the PICS approach revealed prime-side specificity. Enzyme kinetics showed stimulation by Ca2+ and inhibition by Zn2+; variants D70K and H99A confirmed the antagonistic role of the two cation binding sites. Molecular docking and dynamics calculations provided insights into substrate binding and the dual regulation of activity by Ca2+ and Zn2+ through an allosteric surface loop network. X-ray crystallography, positional scanning with fluorogenic tetrapeptides, PICS proteomic substrate profiling, enzyme kinetics, site-directed mutagenesis (D70K, H99A), molecular docking and dynamics Scientific reports High 30013126
2008 KLK8 (neuropsin) is required for a form of synaptic tagging in the hippocampal Schaffer-collateral pathway. A single weak tetanus evokes neuropsin-dependent late associativity that signals through the integrin/actin and L-type voltage-dependent Ca2+ channel (LVDCC) pathway. A second, neuropsin-independent form of synaptic capture is triggered by two tetanic stimuli, but both forms converge on LVDCC. Electrophysiology (LTP recording in hippocampal slices), KLK8 knockout mice, pharmacological inhibition (LVDCC blockers, integrin pathway inhibitors) The Journal of neuroscience High 18216192
2011 Neuropsin (KLK8) is involved in synaptic tagging during LTP at both basal and apical dendritic inputs in hippocampal pyramidal neurons, and is required for synaptic cross-tagging between LTP and LTD at apical dendritic inputs via integrin β1 and CaMKII signaling. Electrophysiology (LTP/LTD recording in hippocampal slices), KLK8 knockout mice, pharmacological inhibition of integrin β1 and CaMKII The Journal of physiology High 21646406
2023 KLK8 proteolytically cleaves the extracellular domain of NCAM1 in hippocampal neurons. Overexpression of KLK8 induces neuronal apoptosis; this is rescued by NCAM1 overexpression or NCAM1 mimetic peptide. KLK8 deficiency prevents CUMS-induced loss of NCAM1 in the hippocampus, placing KLK8-mediated NCAM1 cleavage upstream of neuronal apoptosis in a depression model. Adenovirus-mediated KLK8 overexpression and knockdown in primary hippocampal neurons and HT22 cells, transgenic/KO mice, cleavage assay, immunofluorescence, NCAM1 rescue experiments (overexpression and mimetic peptide) Cell death & disease High 37076499
2025 KLK8 cleaves pro-HGF to release active HGF, which activates the Met/Src/Btk/NF-κB signaling pathway in microglial cells, promoting microglial activation and neuroinflammation. KLK8 overexpression in BV2 microglial cells is sufficient to induce microglial activation. Co-IP coupled with mass spectrometry identified CD44 as a potential KLK8 interactor; KLK8 overexpression decreased CD44 levels. Adenovirus-mediated KLK8 overexpression, Co-immunoprecipitation plus mass spectrometry, pro-HGF cleavage assay, transcriptional profiling, pharmacological Met inhibition, STZ diabetic mouse model, KLK8 knockout mice Theranostics High 40521191
2012 KLK8 can unmask a PAR2 receptor-activating sequence from a synthetic PAR2-derived peptide precursor and can signal via rat PAR2. However, KLK8 does not signal via human PAR2 in HEK or KNRK cells; instead it disarms human PAR1. KLK14, by contrast, signals via both rat and human PAR2. Calcium transient assays, MAPK activation assays, β-arrestin interaction assays, receptor internalization assays, cleavage of synthetic PAR-derived peptide sequences in PAR2-expressing HEK and KNRK cells Biological chemistry Medium 22505524
2021 KLK8 promotes colorectal cancer EMT, proliferation, migration and invasion through a PAR1-dependent pathway. PAR1 antagonist SCH79797 (but not PAR2 antagonist FSLLRY-NH2) attenuated these KLK8-induced effects in vitro and in vivo, placing PAR1 downstream of KLK8 in CRC progression. CCK-8 and colony formation assays, transwell migration/invasion, wound-healing assay, xenograft and metastasis models in nude mice, pharmacological PAR1/PAR2 antagonism, bioinformatics Cell death & disease Medium 34552064
2002 Recombinant neuropsin (KLK8) applied extracellularly enhanced neurite projection from soma at 14 h and promoted neuronal aggregation with neurite fascicles at 48 h in cultured mouse hippocampal neurons, demonstrating a role for extracellular KLK8 in neurite outgrowth and fasciculation. Recombinant neuropsin application to mouse hippocampal neuron cultures, immunolocalization of endogenous neuropsin, morphological analysis Neuroscience letters Medium 11880192
2003 KLK8 (neuropsin)-deficient mice show prolonged recovery of the epidermis after UV-B irradiation, with a thicker stratum corneum and delayed increase in involucrin immunoreactivity (a marker for cell envelope assembly), indicating that KLK8 participates in early epidermal differentiation and cell envelope assembly but not in migration or desquamation per se. KLK8 knockout mice, UV-B irradiation, histomorphology, in situ hybridization for KLK8 mRNA, involucrin immunostaining The British journal of dermatology Medium 14616360
2007 A human-specific T→A mutation (c.71-127T>A) in an intronic region of KLK8 is necessary and sufficient to trigger inclusion of an additional exon, producing the human-specific type II splice form of neuropsin expressed only in human brain and absent from non-human primates. Comparative sequence analysis across primates, in vitro splicing assay, mutation assay Human mutation Medium 17487847
2018 KLK8 (neuropsin) knockdown in mouse primary hippocampal neurons (via siRNA or intra-hippocampal antisense oligonucleotides) reduces MAP2c expression, dendrite length, branching and spine density, and inactivates PKA and downstream pCREB, leading to downregulation of memory-linked genes and impaired memory consolidation. siRNA knockdown in primary hippocampal neurons, intra-hippocampal antisense oligonucleotide administration in vivo, dendritic morphology analysis, Western blot for MAP2c/PKA/pCREB, behavioral memory tests Scientific reports Medium 29967374
2021 Genetic knockdown of murine Klk8 in TgCRND8 Alzheimer's model mice reduces amyloid-β and tau pathology, shifts APP processing toward the non-amyloidogenic pathway, improves neurovascular unit integrity, and enhances microglial Aβ phagocytosis and neuronal Aβ resistance. Genetic cross of TgCRND8 mice with mKlk8+/- mice, amyloid/tau quantification, APP cleavage product analysis, primary glia Aβ phagocytosis assay, primary neuron Aβ resistance assay, behavioral tests Neuropathology and applied neurobiology Medium 33341972
2024 SREBP1 directly transcriptionally regulates KLK8 expression in oral cancer cells (demonstrated by EMSA for SREBF1/KLK8 promoter activity). KLK8 in turn drives CCL22 secretion, promoting regulatory T-cell (Treg) chemotaxis. Ginkgolide B inhibits SREBP1, thereby reducing KLK8 transcription and CCL22 output and suppressing immune escape. EMSA (electrophoretic mobility shift assay), RNA sequencing, SREBP1/KLK8 genetic engineering (overexpression and knockdown), recombinant KLK8 protein treatment, Treg chemotaxis assay, MOC-2 mouse model Phytomedicine Medium 39616730
2024 KLK8 promotes myocardial fibrosis in diabetic cardiomyopathy through PAR1 activation (not PAR2). KLK8 overexpression in cardiac fibroblasts promotes differentiation, collagen synthesis and migration; a PAR1 antagonist (not a PAR2 antagonist) blocks these effects and attenuates TGF-β1/Smad3 signaling. KLK8 overexpression via pEX-1 plasmid and siRNA knockdown in neonatal rat cardiac fibroblasts, PAR1/PAR2 antagonists, collagen synthesis and migration assays, DCM mouse model, molecular docking Chinese medicine Medium 39578836
2025 Age-dependent upregulation of KLK8 in pulmonary endothelial cells promotes endothelial senescence by inactivating the fibronectin/focal adhesion kinase (FAK) pathway, increasing susceptibility of aged mice to ventilator-induced lung injury. KLK8 knockout mice, intra-pulmonary KLK8-overexpressing mice, KLK8 overexpression/knockdown in mouse lung vascular endothelial cells, transcriptome sequencing, senescence assays, FAK pathway analysis, VILI model Aging cell Medium 41310943
2025 Endothelial KLK8 cleaves syndecan-4 (SDC4), contributing to loss of glycocalyx integrity in glomerular endothelial cells. KLK8 also promotes LIFR upregulation, and LIFR signaling mediates glomerular endothelial dysfunction and mesangial cell activation in diabetic nephropathy. Endothelial-specific Klk8 knockout mice show improved albuminuria and glomerulosclerosis in STZ diabetic models. Endothelial-specific KLK8 knockout (Klk8ΔEC) and global KO mice, STZ diabetic model, scRNA-seq, proteomics, SDC4 cleavage assay, KLK8 siRNA in cultured glomerular endothelial cells, lentivirus-Lifr shRNA in vivo, Co-IP bioRxivpreprint Medium
2003 Mouse mast cells express neuropsin (KLK8/Prss19) mRNA and protein, storing it in secretory granules. Expression is upregulated in mucosal mast cells during helminth infection, representing the first identification of neuropsin in an immune cell. cDNA library sequence analysis of BALB/c bone marrow-derived mast cells, kinetic expression studies, immunohistochemistry Biochemical and biophysical research communications Low 12646205
2022 KLK8 overexpression in hypoxia-induced H9c2 cardiomyocytes promotes hypertrophy marker expression (ANP, BNP, MHC7), an effect blocked by the p38 MAPK inhibitor SB202190, placing KLK8 upstream of the p38 MAPK/p53 pathway in right ventricular hypertrophy. KLK8 overexpression and siRNA knockdown in H9c2 cardiomyocytes, pharmacological p38 MAPK inhibition (SB202190), Western blot for hypertrophy markers, HPH rat model Tissue & cell Low 35994918
2026 KLK8 directly interacts with IκBα and promotes its cytoplasmic degradation, leading to p65 nuclear translocation and enhanced NF-κB activity, and stimulates NLRP3 inflammasome activation (increased NLRP3, ASC, cleaved Caspase-1) in IL-1β-stimulated chondrocytes, promoting cartilage degradation and pyroptosis in osteoarthritis. KLK8 siRNA knockdown in IL-1β-stimulated chondrocytes, direct interaction assay with IκBα, Western blot for NF-κB pathway components and NLRP3 inflammasome, flow cytometry for pyroptosis, ELISA for cytokines, MLI-induced OA mouse model Tissue & cell Low 41793791
2002 KLK8 mRNA expression is upregulated in hyperkeratotic skin conditions (psoriasis vulgaris, seborrheic keratosis, lichen planus, squamous cell carcinoma) and correlates with keratinocyte terminal differentiation induced by high calcium in cell culture, indicating a role in epidermal terminal differentiation. Northern blot, in situ hybridization of normal and pathological human skin samples, calcium-induced differentiation in keratinocyte cultures Molecular pathology Low 12147714

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Human alpha-defensin 1 (HNP-1) inhibits adenoviral infection in vitro. Regulatory peptides 132 11495691
2005 Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study. BMC cancer 127 15656915
1996 Intramolecular inhibition of human defensin HNP-1 by its propiece. The Journal of clinical investigation 111 8601627
1997 Differential scanning microcalorimetry indicates that human defensin, HNP-2, interacts specifically with biomembrane mimetic systems. Biochemistry 87 9063901
1996 Interactions of monomeric rabbit neutrophil defensins with bilayers: comparison with dimeric human defensin HNP-2. Biochemistry 76 8794771
2009 ADP-ribosylation of human defensin HNP-1 results in the replacement of the modified arginine with the noncoded amino acid ornithine. Proceedings of the National Academy of Sciences of the United States of America 44 19897717
2007 Antimicrobial activity of truncated alpha-defensin (human neutrophil peptide (HNP)-1) analogues without disulphide bridges. Molecular immunology 44 17548109
2013 Alarmin HNP-1 promotes pyroptosis and IL-1β release through different roles of NLRP3 inflammasome via P2X7 in LPS-primed macrophages. Innate immunity 41 23792296
2010 Resonance assignment and three-dimensional structure determination of a human alpha-defensin, HNP-1, by solid-state NMR. Journal of molecular biology 36 20097206
2008 Neuropsin (KLK8)-dependent and -independent synaptic tagging in the Schaffer-collateral pathway of mouse hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 18216192
2023 Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1. Cell death & disease 32 37076499
2004 The novel serine protease tumor-associated differentially expressed gene-14 (KLK8/Neuropsin/Ovasin) is highly overexpressed in cervical cancer. American journal of obstetrics and gynecology 31 14749636
2002 Epidermal expression of serine protease, neuropsin (KLK8) in normal and pathological skin samples. Molecular pathology : MP 31 12147714
2021 KLK8 promotes the proliferation and metastasis of colorectal cancer via the activation of EMT associated with PAR1. Cell death & disease 30 34552064
2016 Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer. Biological chemistry 30 27483364
2008 Differential signaling mechanisms of HNP-induced IL-8 production in human lung epithelial cells and monocytes. Journal of cellular physiology 29 17786963
2010 MDP-NOD2 stimulation induces HNP-1 secretion, which contributes to NOD2 antibacterial function. Inflammatory bowel diseases 28 19856414
2017 Transition to an Aquatic Habitat Permitted the Repeated Loss of the Pleiotropic KLK8 Gene in Mammals. Genome biology and evolution 27 29145610
2002 Extracellular serine protease neuropsin (KLK8) modulates neurite outgrowth and fasciculation of mouse hippocampal neurons in culture. Neuroscience letters 27 11880192
2007 A human-specific mutation leads to the origin of a novel splice form of neuropsin (KLK8), a gene involved in learning and memory. Human mutation 23 17487847
1994 Localization of human neutrophil peptide (HNP) and its messenger RNA in neutrophil series. Annals of hematology 23 8080882
2003 Prolonged recovery of ultraviolet B-irradiated skin in neuropsin (KLK8)-deficient mice. The British journal of dermatology 20 14616360
2012 Proteinase-activated receptors (PARs): differential signalling by kallikrein-related peptidases KLK8 and KLK14. Biological chemistry 19 22505524
2011 Diversity of neuropsin (KLK8)-dependent synaptic associativity in the hippocampal pyramidal neuron. The Journal of physiology 19 21646406
2010 Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice. Biological chemistry 16 20180635
2006 Expression of tumor-associated differentially expressed Gene-14 (TADG-14/KLK8) and its protein hK8 in uterine endometria and endometrial carcinomas. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 16888409
1989 Imaging of small cell carcinoma using 131I-labelled antibodies to vasopressin associated human neurophysin (VP-HNP). Nuclear medicine communications 14 2559381
2018 Structural determinants of specificity and regulation of activity in the allosteric loop network of human KLK8/neuropsin. Scientific reports 13 30013126
2018 A serine protease KLK8 emerges as a regulator of regulators in memory: Microtubule protein dependent neuronal morphology and PKA-CREB signaling. Scientific reports 12 29967374
2016 LL-37, HNP-1, and HBD2/3 modulate the secretion of cytokines TNF-α, IL-6, IFN-γ, IL-10 and MMP1 in human primary cell cultures. European cytokine network 12 27910811
2021 LncRNA KLK8 modulates stem cell characteristics in colon cancer. Pathology, research and practice 11 34271345
2004 Regulation of activities of NK cells and CD4 expression in T cells by human HNP-1, -2, and -3. Biochemical and biophysical research communications 11 15369771
2022 Recombinant HNP-1 Produced by Escherichia coli Triggers Bacterial Apoptosis and Exhibits Antibacterial Activity against Drug-Resistant Bacteria. Microbiology spectrum 10 35019682
2022 Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19. International journal of molecular sciences 9 35408809
2021 Genetic knockdown of Klk8 has sex-specific multi-targeted therapeutic effects on Alzheimer's pathology in mice. Neuropathology and applied neurobiology 9 33341972
2021 DNA methylation of the KLK8 gene in depression symptomatology. Clinical epigenetics 7 34715912
2010 Altered serum levels of human neutrophil peptides (HNP) and human beta-defensin 2 (hBD2) in Wegener's granulomatosis. Rheumatology international 7 21132301
2008 LDL oxidation by THP-1 monocytes: implication of HNP-1, SgIII and DMT-1. Clinica chimica acta; international journal of clinical chemistry 7 19150442
2004 The alpha-defensins HNP-1 and HNP-2 are dominant self-peptides presented by HLA class-II molecules in lesional psoriatic skin. European journal of dermatology : EJD 7 15246937
2025 HNP-1: From Structure to Application Thanks to Multifaceted Functions. Microorganisms 6 40005828
2025 KLK8/HGF/Met signaling pathway mediates diabetes-associated hippocampal neuroinflammation in male mice. Theranostics 6 40521191
2024 The potential immunotherapy effect of Ginkgolide B thwarts oral squamous cell carcinoma progression by targeting the SREBP1/KLK8/CCL22 axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 6 39616730
2015 The therapeutic impact of HNP-1 in condyloma acuminatum. International journal of dermatology 6 25600882
2023 circSSPO boosts growth of esophageal squamous cell carcinoma through upregulation of micrRNA-6820-5p-mediated KLK8 and PKD1 expression. Cell biology and toxicology 5 37812360
2020 Computational evaluation of modified peptides from human neutrophil peptide 1 (HNP-1). Journal of biomolecular structure & dynamics 5 32981420
2019 Newly Identified HNP-F from Human Neutrophil Peptide-1 Promotes Hemostasis. Biotechnology journal 5 30927490
2010 HNP-3 enhanced the antimicrobial activity of CIP by promoting ATP efflux from P. aeruginosa cells. Molecular biology reports 5 21107732
2003 Mouse mast cells express the tryptic protease neuropsin/Prss19. Biochemical and biophysical research communications 5 12646205
2024 Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma. BMC pulmonary medicine 3 38273291
2022 Lactoferrin and Human Neutrophil Protein (HNP) 1-3 Levels During the Neonatal Period in Preterm Infants. Frontiers in pediatrics 3 35967550
2022 Kallikrein-related peptidase-8 (KLK8) aggravated hypoxia-induced right ventricular hypertrophy by targeting P38 MAPK/P53 signaling pathway. Tissue & cell 3 35994918
2024 Sex-Specific Differences in Serum Kallikrein-8 (KLK8): An Exploratory Study. Journal of Alzheimer's disease : JAD 2 38995781
2024 Gastrodin attenuates diabetic cardiomyopathy characterized by myocardial fibrosis by inhibiting the KLK8-PAR1 signaling axis. Chinese medicine 2 39578836
2025 Transcriptomic and Molecular Insights into the Response of Multidrug-Resistant Helicobacter pylori to Human Neutrophil Peptide 1 (HNP-1). Probiotics and antimicrobial proteins 1 40938539
2025 Structural and mechanistic divergence in LL-37, HNP-1, and Magainin-2: An integrated computational and biophysical analysis. Current research in structural biology 1 41376844
2024 Inhibition of KLK8 promotes pulmonary endothelial repair by restoring the VE-cadherin/Akt/FOXM1 pathway. Journal of pharmaceutical analysis 1 40291017
2026 KLK8 promotes cartilage degradation and pyroptosis in osteoarthritis by activating the NF-κB and NLRP3 inflammasome pathways. Tissue & cell 0 41793791
2026 Heteroaggregation of Antimicrobial Peptides LL-37 and HNP‑1 Drives Cooperative Neutralization of Cytotoxicity. JACS Au 0 41889757
2026 Capsule and PspA Cooperatively Confer Resistance of Streptococcus pneumoniae to the Human Defensin HNP-1. International journal of molecular sciences 0 41977167
2025 Age-Dependent KLK8 Upregulation Contributes to Elevated Susceptibility to Ventilator-Induced Lung Injury in the Elderly Mice. Aging cell 0 41310943
2014 Behavior of calf Sertoli cells and fibroblast cells transfected with the human HNP-1 gene. Genetics and molecular research : GMR 0 25501177
2000 [Regeneration of HNP transgenic alfalfa plants by Agrobacterium mediated gene transfer]. Yi chuan xue bao = Acta genetica Sinica 0 11147352

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