ArticleJournal of the American Society of Nephrology : JASN2010
PKC-delta promotes renal tubular cell apoptosis associated with proteinuria.
Article in Journal of the American Society of Nephrology : JASN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers.Scientific reports · 2019Trial
- Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation.Journal of advanced research · 2026Article
- Tubulointerstitial inflammation and fibrosis induced by proteinuria: fresh insights.Frontiers in pharmacology · 2026Review
- Xian Huang Fang Inhibits the PKCδ/MAPK Signaling Pathway to Attenuate Renal Tubular Epithelial Cell Senescence and Thereby Delay Renal Interstitial Fibrosis.Drug design, development and therapy · 2025Article
- Immune-mediated renal injury in diabetic kidney disease: from mechanisms to therapy.Frontiers in immunology · 2025Review
- Inhibition of PKC-δ retards kidney fibrosis via inhibiting cGAS-STING signaling pathway in mice.Cell death discovery · 2024Article
- Upregulation of rate-limiting enzymes in cholesterol metabolism by PKCδ mediates endothelial apoptosis in diabetic wound healing.Cell death discovery · 2024Article
- Tubulointerstitial injury in proteinuric chronic kidney diseases.Frontiers in medicine · 2024Review
- Loss of S1P Lyase Expression in Human Podocytes Causes a Reduction in Nephrin Expression That Involves PKCδ Activation.International journal of molecular sciences · 2023Article
- Non-diabetic urine glucose in idiopathic membranous nephropathy.Renal failure · 2022Article
- Article
- Establishment and validation of the cut-off values of estimated glomerular filtration rate and urinary albumin-to-creatinine ratio for diabetic kidney disease: A multi-center, prospective cohort study.Frontiers in endocrinology · 2022Observational
- Tubular mitochondrial AKT1 is activated during ischemia reperfusion injury and has a critical role in predisposition to chronic kidney disease.Kidney international · 2021Article
- Protein Kinase C-Journal of the American Society of Nephrology : JASN · 2020Article
- p53 upregulated by HIF-1α promotes hypoxia-induced G2/M arrest and renal fibrosis in vitro and in vivo.Journal of molecular cell biology · 2019Article
- Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity.Bioscience reports · 2018Article
- Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria.Bioscience reports · 2018Article
- Mitochondrial oxidative stress activates COX-2/mPGES-1/PGE2 cascade induced by albumin in renal proximal tubular cells.Oncotarget · 2018Article
- AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms.Kidney international · 2017Review
- Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice.Scientific reports · 2017Article
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7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteinuria may contribute to progressive renal damage by inducing tubulointerstitial inflammation, fibrosis, and tubular cell injury and death, but the mechanisms underlying these pathologic changes remain largely unknown. Here, in a rat kidney proximal tubular cell line (RPTC), albumin induced apoptosis in a time- and dose-dependent manner. Caspase activation accompanied albumin-induced apoptosis, and general caspase inhibitors could suppress this activation. In addition, Bcl-2 transfection inhibited apoptosis and attenuated albumin-induced Bax translocation to mitochondria and cytochrome c release from the organelles, further confirming a role for the intrinsic pathway of apoptosis in albuminuria-associated tubular apoptosis. We observed phosphorylation and activation of PKC-delta early during treatment of RPTC cells with albumin. Rottlerin, a pharmacologic inhibitor of PKC-delta, suppressed albumin-induced Bax translocation, cytochrome c release, and apoptosis. Moreover, a dominant-negative mutant of PKC-delta blocked albumin-induced apoptosis in RPTC cells. In vivo, we observed activated PKC-delta in proteinuric kidneys of streptozotocin-induced diabetic mice and in kidneys after direct albumin overload. Notably, albumin overload induced apoptosis in renal tubules, which was less severe in PKC-delta-knockout mice. Taken together, these results suggest that activation of PKC-delta promotes tubular cell injury and death during albuminuria, broadening our understanding of the pathogenesis of progressive proteinuric kidney diseases.
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