ArticleThe Journal of clinical investigation2015
Gq signaling causes glomerular injury by activating TRPC6.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 66 citations in OpenAlex.
- Urotensin II Receptor Deletion Mitigates Kidney Injury and Renal Lipid Remodeling in Mice Fed a Long-Term High-Fat Diet.FASEB bioAdvances · 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
- Analytical methods in studying cell force sensing: principles, current technologies and perspectives.Regenerative biomaterials · 2025Review
- Article
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation.iScience · 2023Article
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- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- 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
- Efficacy and Safety of Tacrolimus in the Treatment of Pediatric Henoch-Schönlein Purpura Nephritis.Paediatric drugs · 2022Article
- Article
- Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy.Journal of diabetes research · 2022Article
- Insulin-activated store-operated CaNature communications · 2021Article
- Blockade of the natriuretic peptide clearance receptor attenuates proteinuria in a mouse model of focal segmental glomerulosclerosis.Physiological reports · 2021Article
- Crosstalk between Renal and Vascular Calcium Signaling: The Link between Nephrolithiasis and Vascular Calcification.International journal of molecular sciences · 2021Review
- WNT-β-catenin signalling - a versatile player in kidney injury and repair.Nature reviews. Nephrology · 2021Review
- GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity.Theranostics · 2021Article
- Role of opioid signaling in kidney damage during the development of salt-induced hypertension.Life science alliance · 2020Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
Familial forms of focal segmental glomerulosclerosis (FSGS) have been linked to gain-of-function mutations in the gene encoding the transient receptor potential channel C6 (TRPC6). GPCRs coupled to Gq signaling activate TRPC6, suggesting that Gq-dependent TRPC6 activation underlies glomerular diseases. Here, we developed a murine model in which a constitutively active Gq α subunit (Gq(Q209L), referred to herein as GqQ>L) is specifically expressed in podocytes and examined the effects of this mutation in response to puromycin aminonucleoside (PAN) nephrosis. We found that compared with control animals, animals expressing GqQ>L exhibited robust albuminuria, structural features of FSGS, and reduced numbers of glomerular podocytes. Gq activation stimulated calcineurin (CN) activity, resulting in CN-dependent upregulation of TRPC6 in murine kidneys. Deletion of TRPC6 in GqQ>L-expressing mice prevented FSGS development and inhibited both tubular damage and podocyte loss induced by PAN nephrosis. Similarly, administration of the CN inhibitor FK506 reduced proteinuria and tubular injury but had more modest effects on glomerular pathology and podocyte numbers in animals with constitutive Gq activation. Moreover, these Gq-dependent effects on podocyte injury were generalizable to diabetic kidney disease, as expression of GqQ>L promoted albuminuria, mesangial expansion, and increased glomerular basement membrane width in diabetic mice. Together, these results suggest that targeting Gq/TRPC6 signaling may have therapeutic benefits for the treatment of glomerular diseases.
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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.