ArticleJournal of the American Society of Nephrology : JASN2009
PKC-beta1 mediates glucose-induced Akt activation and TGF-beta1 upregulation in mesangial cells.
Article in Journal of the American Society of Nephrology : JASN, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 108 citations in OpenAlex.
- Molecular pathways and emerging therapeutic targets in the pathogenesis of diabetic kidney disease.Frontiers in physiology · 2026Review
- Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation.BMC cancer · 2025Article
- PKCα Activation via the Thyroid Hormone Membrane Receptor Is Key to Thyroid Cancer Growth.International journal of molecular sciences · 2024Article
- Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ERα+ breast cancer.NPJ breast cancer · 2023Article
- Cell surface GRP78 regulates TGFβ1-mediated profibrotic responsesFrontiers in pharmacology · 2023Article
- YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosisFrontiers in pharmacology · 2023Article
- Integrin β1/Cell Surface GRP78 Complex Regulates TGFβ1 and Its Profibrotic Effects in Response to High Glucose.Biomedicines · 2022Article
- Current Strategies and Potential Prospects for Nanoparticle-Mediated Treatment of Diabetic Nephropathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Review
- Anti-Apoptosis of Podocytes and Pro-Apoptosis of Mesangial Cells for Telmisartan in Alleviating Diabetic Kidney Injury.Frontiers in pharmacology · 2022Article
- MicroRNA‑218 inhibits the malignant phenotypes of glioma by modulating the TNC/AKT/AP‑1/TGFβ1 feedback signaling loop.International journal of molecular medicine · 2021Article
- Activators and Inhibitors of Protein Kinase C (PKC): Their Applications in Clinical Trials.Pharmaceutics · 2021Review
- High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct.Scientific reports · 2021Article
- Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy.International journal of molecular sciences · 2021Article
- Bone Cells Differentiation: How CFTR Mutations May Rule the Game of Stem Cells Commitment?Frontiers in cell and developmental biology · 2021Review
- LncRNA ARAP1-AS2 promotes high glucose-induced human proximal tubular cell injury via persistent transactivation of the EGFR by interacting with ARAP1.Journal of cellular and molecular medicine · 2020Article
- Retinal Physiology and Circulation: Effect of Diabetes.Comprehensive Physiology · 2020Review
- Recent Insights Into SREBP as a Direct Mediator of Kidney Fibrosis via Lipid-Independent Pathways.Frontiers in pharmacology · 2020Review
- Cell surface expression of 78-kDa glucose-regulated protein (GRP78) mediates diabetic nephropathy.The Journal of biological chemistry · 2019Article
- Branched Chain Amino Acids Protects Rat Mesangial Cells from High Glucose by Modulating TGF-β1 and BMP-7.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- H2S attenuates the myocardial fibrosis in diabetic rats through modulating PKC-ERK1/2MAPK signaling pathway.Technology and health care : official journal of the European Society for Engineering and Medicine · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of glomerular matrix is a hallmark of diabetic nephropathy. The serine/threonine kinase Akt mediates glucose-induced upregulation of collagen I in mesangial cells through transactivation of the EGF receptor (EGFR). In addition, in renal tubular cells, glucose-induced secretion of TGF-beta requires phosphoinositide-3-OH kinase, suggesting a possible role for Akt in the modulation of TGF-beta expression, but the mechanisms of Akt activation and its involvement in TGF-beta regulation are unknown. Here, in primary mesangial cells, high glucose induced AktS473 phosphorylation, which correlates with its activation, in a protein kinase C beta (PKC-beta)-dependent manner. Glucose led to PKC-beta1 membrane translocation and association with Akt, and PKC-beta1 immunoprecipitated from glucose-treated cells phosphorylated recombinant Akt on S473. PKC is known to mediate glucose-induced TGF-beta1 upregulation through the transcription factor AP-1; here, inhibitors of phosphoinositide-3-OH kinase, PKC-beta and Akt, and dominant-negative Akt all prevented glucose-induced activation of AP-1 and upregulation of TGF-beta1. Finally, pharmacologic and dominant negative inhibition of EGFR blocked glucose-induced activation of PKC-beta1, phosphorylation of AktS473, activation of AP-1, and upregulation of TGF-beta1. In vivo, the PKC-beta inhibitor ruboxistaurin prevented Akt activation in the renal cortex of diabetic rats. In conclusion, PKC-beta1 is an Akt S473 kinase in glucose-treated mesangial cells, and TGF-beta1 transcriptional upregulation requires EGFR/PKC-beta1/Akt signaling. New therapeutic approaches for diabetic nephropathy may result from targeting components of this pathway, particularly the initial EGFR transactivation.
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