ArticleThe Journal of biological chemistry2008
Hepatocyte growth factor suppresses proinflammatory NFkappaB activation through GSK3beta inactivation in renal tubular epithelial cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Molecular mechanisms in lithium-associated renal disease: a systematic review.International urology and nephrology · 2016Pooled it
- Dexamethasone enhances intestinal glucose absorption and TMPRSS2 expression with implications for hyperglycaemia and infection risk.Scientific reports · 2025Article
- Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.Clinical science (London, England : 1979) · 2025Review
- Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles.Bioactive materials · 2023Article
- Development of (4-Phenylamino)quinazoline Alkylthiourea Derivatives as Novel NF-κB Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2022Article
- S100A16 promotes acute kidney injury by activating HRD1-induced ubiquitination and degradation of GSK3β and CK1α.Cellular and molecular life sciences : CMLS · 2022Article
- Therapeutic Targeting of GSK3β-Regulated Nrf2 and NFκB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis.Frontiers in medicine · 2022Article
- Understanding the Renal Fibrotic Process in Leptospirosis.International journal of molecular sciences · 2021Review
- Permissive effect of GSK3β on profibrogenic plasticity of renal tubular cells in progressive chronic kidney disease.Cell death & disease · 2021Article
- Alpinia oxyphylla-Schisandra chinensis Herb Pair Alleviates Amyloid-β Induced Cognitive Deficits via PI3K/Akt/Gsk-3β/CREB Pathway.Neuromolecular medicine · 2020Article
- Review
- Article
- Follicle-stimulating hormone promotes renal tubulointerstitial fibrosis in aging women via the AKT/GSK-3β/β-catenin pathway.Aging cell · 2019Article
- GSK3β-mediated Keap1-independent regulation of Nrf2 antioxidant response: A molecular rheostat of acute kidney injury to chronic kidney disease transition.Redox biology · 2019Article
- Fibroblast-SpecificJournal of the American Society of Nephrology : JASN · 2018Article
- GSK-3β activation index is a potential indicator for recurrent inflammation of chronic rhinosinusitis without nasal polyps.Journal of cellular and molecular medicine · 2017Article
- Valproate hampers podocyte acquisition of immune phenotypes via intercepting the GSK3β facilitated NFkB activation.Oncotarget · 2017Article
- Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in sepsis.Journal of nephrology · 2017Article
- Correlation between PKB/Akt, GSK-3β expression and tubular epithelial-mesenchymal transition in renal allografts with chronic active antibody-mediated rejection.Experimental and therapeutic medicine · 2017Article
- Genetic and Pharmacologic Targeting of Glycogen Synthase Kinase 3β Reinforces the Nrf2 Antioxidant Defense against Podocytopathy.Journal of the American Society of Nephrology : JASN · 2016Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Activation of NFkappaB is a fundamental cellular event central to all inflammatory diseases. Hepatocyte growth factor (HGF) ameliorates both acute and chronic inflammation in a multitude of organ systems through modulating NFkappaB activity; nevertheless, the exact molecular mechanism remains uncertain. Here we report that HGF through inactivation of GSK3beta suppresses NFkappaB p65 phosphorylation specifically at position Ser-468. The Ser-468 of RelA/p65 situates in a GSK3beta consensus motif and could be directly phosphorylated by GSK3beta both in vivo and in vitro, signifying Ser-468 of RelA/p65 as a putative substrate for GSK3beta. In addition, the C terminus of RelA/p65 harbors a highly conserved domain homologue of the consensus docking sequence for GSK3beta. Moreover, this domain was required for efficient phosphorylation of Ser-468 and was indispensable for the physical interaction between RelA/p65 and GSK3beta. HGF substantially intercepted this interaction by inactivating GSK3beta. Functionally, phosphorylation of Ser-468 of RelA/p65 was required for the induced expression of a particular subset of proinflammatory NFkappaB-dependent genes. Diminished phosphorylation at Ser-468 by HGF resulted in a gene-specific inhibition of these genes' expression. The action of HGF on proinflammatory NFkappaB activation was consistently mimicked by a selective GSK3beta inhibitor or GSK3beta knockdown by RNA interference but largely abrogated in cells expressing the mutant uninhibitable GSK3beta. Collectively, our findings suggest that HGF has a potent suppressive effect on NFkappaB activation, which is mediated by GSK3beta, an important signaling transducer controlling RelA/p65 phosphorylation specificity and directing the transcription of selective proinflammatory cytokines implicated in inflammatory kidney disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.