ArticleAmerican journal of physiology. Cell physiology2009
TRPC6 mutations associated with focal segmental glomerulosclerosis cause constitutive activation of NFAT-dependent transcription.
Article in American journal of physiology. Cell physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
96 citing papers in PubMed, 179 citations in OpenAlex.
- Genetic mutation patterns in Indonesian children with primary steroid-resistant nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Article
- Treatment outcomes and ongoing pediatric trials in steroid-resistant nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Review
- Gain-of-Function VariantCirculation. Genomic and precision medicine · 2026Article
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- Genotype-phenotype correlations and clinical outcomes of genetic TRPC6 podocytopathies.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Observational
- TRPC6 effects on albumin permeation, nephrin shedding, and apoptosis in podocytes: Role of calcineurin and metalloproteases.Physiological reports · 2025Article
- Impact of immune cell metabolism on membranous nephropathy and prospective therapy.Communications biology · 2025Review
- When should the nephrologist think about genetics in patients with glomerular diseases?Clinical kidney journal · 2025Review
- Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy.Journal of the American Society of Nephrology : JASN · 2025Article
- Article
- Novel Pathogenic Mutation of P209L in TRPC6 Gene Causes Adult Focal Segmental Glomerulosclerosis.Biochemical genetics · 2024Article
- Review
- Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024Review
- Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation.International journal of molecular sciences · 2023Review
- Mechanotransduction via endothelial adhesion molecule CD31 initiates transmigration and reveals a role for VEGFR2 in diapedesis.Immunity · 2023Article
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy.Frontiers in immunology · 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
- TRPC6 N338S is a gain-of-function mutant identified in patient with doxorubicin-induced cardiotoxicity.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the canonical transient receptor potential channel TRPC6 lead to an autosomal dominant form of human kidney disease characterized histologically by focal and segmental glomerulosclerosis. Several of these mutations enhance the amplitude and duration of the channel current. However, the effect of these mutations on the downstream target of TRPC6, the nuclear factor of activated T cell (NFAT) transcription factors, has not been previously examined. Here we demonstrate that all three TRPC6 mutations previously shown to enhance channel activity lead to enhanced basal NFAT-mediated transcription in several cell lines, including cultured podocytes. These effects are dependent on channel activity and are dominant when mutants are coexpressed with wild-type TRPC6. While TRPC6 mutants do not demonstrate an increase in basal channel currents, a subset of cells expressing the R895C and E897K mutants have elevated basal calcium levels as measured by Fura-2 imaging. Activation of NFAT by TRPC6 mutants is blocked by inhibitors of calcineurin, calmodulin-dependent kinase II, and phosphatidylinositol 3-kinase. PP2 partially inhibits NFAT activation by mutant TRPC6 independently of Src, Yes, or Fyn. Differences in channel glycosylation and surface expression do not explain the ability of mutants to enhance NFAT activation. Taken together, these results identify the activation of the calcineurin-NFAT pathway as a potential mediator of focal segmental glomerulosclerosis.
Indexed as
Identifiers
What OpenQuestion holds
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.