ArticleKidney international2019
Knockout of TRPC6 promotes insulin resistance and exacerbates glomerular injury in Akita mice.
Article in Kidney international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Association between triglyceride glucose index and risk of acute kidney injury in critically ill patients: a systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Transient receptor potential canonical (TRPC) channels in diabetes and associated complications.Channels (Austin, Tex.) · 2026Review
- Urotensin II Receptor Deletion Mitigates Kidney Injury and Renal Lipid Remodeling in Mice Fed a Long-Term High-Fat Diet.FASEB bioAdvances · 2026Article
- TRPC6 loss triggers mitochondrial dysfunction that drives white adipose tissue vulnerability to obesity and insulin resistance.Experimental & molecular medicine · 2026Article
- Podocyte specific knockout (KO) of the natriuretic peptide clearance receptor (NPRC) attenuates diabetic kidney disease (DKD).Physiological reports · 2026Article
- Podocyte specific knockout of the natriuretic peptide clearance receptor is podocyte protective in focal segmental glomerulosclerosis.PloS one · 2025Article
- Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy.Renal failure · 2024Article
- Recent advancement of sonogenetics: A promising noninvasive cellular manipulation by ultrasound.Genes & diseases · 2024Review
- The activation of spliced X-box binding protein 1 by isorhynchophylline therapy improves diabetic encephalopathy.Cell biology and toxicology · 2023Article
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Podocyte protease activated receptor 1 stimulation in mice produces focal segmental glomerulosclerosis mirroring human disease signaling events.Kidney international · 2023Article
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Limonin, a natural ERK2 agonist, protects against ischemic acute kidney injury.International journal of biological sciences · 2023Article
- Microarray Expression Profile of Exosomal circRNAs from High Glucose Stimulated Human Renal Tubular Epithelial Cells.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Transient receptor potential canonical 6 knockdown ameliorated diabetic kidney disease by inhibiting nuclear factor of activated T cells 2 expression in glomerular mesangial cells.Renal failure · 2022Article
- The Effects of TRPC6 Knockout in Animal Models of Kidney Disease.Biomolecules · 2022Review
- Transcriptional regulatory networks of circulating immune cells in type 1 diabetes: A community knowledgebase.iScience · 2022Article
- Article
- Advances in TRP channel drug discovery: from target validation to clinical studies.Nature reviews. Drug discovery · 2022Review
- Article
Corrections and comments
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- Erratum issued
Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Gain-of-function mutations in TRPC6 cause familial focal segmental glomerulosclerosis, and TRPC6 is upregulated in glomerular diseases including diabetic kidney disease. We studied the effect of systemic TRPC6 knockout in the Akita model of type 1 diabetes. Knockout of TRPC6 inhibited albuminuria in Akita mice at 12 and 16 weeks of age, but this difference disappeared by 20 weeks. Knockout of TRPC6 also reduced tubular injury in Akita mice; however, mesangial expansion was significantly increased. Hyperglycemia and blood pressure were similar between TRPC6 knockout and wild-type Akita mice, but knockout mice were more insulin resistant. In cultured podocytes, knockout of TRPC6 inhibited expression of the calcium/calcineurin responsive gene insulin receptor substrate 2 and decreased insulin responsiveness. Insulin resistance is reported to promote diabetic kidney disease independent of blood glucose levels. While the mechanisms are not fully understood, insulin activates both Akt2 and ERK, which inhibits apoptosis signal regulated kinase 1 (ASK1)-p38-induced apoptosis. In cultured podocytes, hyperglycemia stimulated p38 signaling and induced apoptosis, which was reduced by insulin and ASK1 inhibition and enhanced by Akt or ERK inhibition. Glomerular p38 signaling was increased in TRPC6 knockout Akita mice and was associated with enhanced expression of the p38 gene target cyclooxygenase 2. These data suggest that knockout of TRPC6 in Akita mice promotes insulin resistance and exacerbates glomerular disease independent of hyperglycemia.
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