ArticleThe Journal of clinical investigation2015
Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis.
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 60 papers, 3 of them syntheses that pooled it.
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Who cites it
60 citing papers in PubMed, 3 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Genome-Wide Association Study for eGFR in a Taiwanese Population.Clinical journal of the American Society of Nephrology : CJASN · 2022Pooled it
- Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal Fibrosis.Journal of the American Society of Nephrology : JASN · 2017Pooled it
- Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.Kidney international · 2015Pooled it
- APOL1 risk alleles modulate T cell receptor signaling to promote allograft rejection.The Journal of clinical investigation · 2026Article
- Decoding the Evolution and Co-Phospho-Regulatory Networks of SHROOM Proteins.Journal of molecular evolution · 2026Article
- Design of precision therapeutics for a CKD risk allele by targeting Shroom3-Rock interaction.Nature communications · 2025Article
- Non-HLA Genetics and Application to Living Donor Candidates.Current transplantation reports · 2025Article
- Mapping Shroom3 expression across the adult mouse.Gene expression patterns : GEP · 2025Article
- Article
- The growth hormone/IGF-1 axis is a risk factor for long-term kidney allograft failure.JCI insight · 2025Article
- Alternative Splicing in Mechanically Stretched Podocytes as a Model of Glomerular Hypertension.Journal of the American Society of Nephrology : JASN · 2025Article
- Focus on a CKD-Associated Locus:Kidney international reports · 2025Article
- Clinical and Metabolic Signatures ofKidney international reports · 2025Article
- Shroom3-Rock interaction and profibrotic function: Resolving mechanism of an intronic CKD risk allele.bioRxiv : the preprint server for biology · 2024Article
- Multi-Omics Integration in Nephrology: Advances, Challenges, and Future Directions.Seminars in nephrology · 2024Review
- Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.Nature genetics · 2024Article
- Advancing mouse models for transplantation research.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
- The Critical Role of the Shroom Family Proteins in Morphogenesis, Organogenesis and Disease.Phenomics (Cham, Switzerland) · 2024Review
- Genome-wide association studies reconstructing chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- External proficiency testing for histocompatibility and immunogenetics in today and future.Frontiers in genetics · 2024Review
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
Fibrosis underlies the loss of renal function in patients with chronic kidney disease (CKD) and in kidney transplant recipients with chronic allograft nephropathy (CAN). Here, we studied the effect of an intronic SNP in SHROOM3, which has previously been linked to CKD, on the development of CAN in a prospective cohort of renal allograft recipients. The presence of the rs17319721 allele at the SHROOM3 locus in the donor correlated with increased SHROOM3 expression in the allograft. In vitro, we determined that the sequence containing the risk allele at rs17319721 is a transcription factor 7-like 2-dependent (TCF7L2-dependent) enhancer element that functions to increase SHROOM3 transcription. In renal tubular cells, TGF-β1 administration upregulated SHROOM3 expression in a β-catenin/TCF7L2-mediated manner, while SHROOM3 in turn facilitated canonical TGF-β1 signaling and increased α1 collagen (COL1A1) expression. Inducible and tubular cell-specific knockdown of Shroom3 markedly abrogated interstitial fibrosis in mice with unilateral ureteric obstruction. Moreover, SHROOM3 expression in allografts at 3 months after transplant and the presence of the SHROOM3 risk allele in the donor correlated with increased allograft fibrosis and with reduced estimated glomerular filtration rate at 12 months after transplant. Our findings suggest that rs17319721 functions as a cis-acting expression quantitative trait locus of SHROOM3 that facilitates TGF-β1 signaling and contributes to allograft injury.
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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.