ArticleThe Journal of clinical investigation2014
Podocyte-specific RAP1GAP expression contributes to focal segmental glomerulosclerosis-associated glomerular injury.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Shared genetic correlations between kidney diseases and sepsis.Frontiers in endocrinology · 2024Pooled it
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- Identification and validation of biomarkers in membranous nephropathy and pan-cancer analysis.Frontiers in immunology · 2024Article
- Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway.BMC complementary medicine and therapies · 2023Article
- Identification of core genes and pathways between geriatric multimorbidity and renal insufficiency: potential therapeutic agents discovered using bioinformatics analysis.BMC medical genomics · 2022Article
- Rap1 Activity Is Essential for Focal Adhesion and Slit Diaphragm Integrity.Frontiers in cell and developmental biology · 2022Article
- DACH1 as a multifaceted and potentially druggable susceptibility factor for kidney disease.The Journal of clinical investigation · 2021Article
- DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity.The Journal of clinical investigation · 2021Article
- Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury.International journal of biological sciences · 2020Article
- Disruption of MAGI2-RapGEF2-Rap1 signaling contributes to podocyte dysfunction in congenital nephrotic syndrome caused by mutations in MAGI2.Kidney international · 2019Article
- Nephrin Signaling Results in IntegrinJournal of the American Society of Nephrology : JASN · 2019Article
- Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study Loci.Journal of the American Society of Nephrology : JASN · 2019Article
- Methylation level of Rap1GAP and the clinical significance in MDS.Oncology letters · 2018Article
- Molecular Mechanisms of Injury in HIV-Associated Nephropathy.Frontiers in medicine · 2018Review
- Variations in MicroRNA-25 Expression Influence the Severity of Diabetic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2017Article
- The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Dynamin Autonomously Regulates Podocyte Focal Adhesion Maturation.Journal of the American Society of Nephrology : JASN · 2017Article
- MAGI-1 Interacts with Nephrin to Maintain Slit Diaphragm Structure through Enhanced Rap1 Activation in Podocytes.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Injury to the specialized epithelial cells of the glomerulus (podocytes) underlies the pathogenesis of all forms of proteinuric kidney disease; however, the specific genetic changes that mediate podocyte dysfunction after injury are not fully understood. Here, we performed a large-scale insertional mutagenic screen of injury-resistant podocytes isolated from mice and found that increased expression of the gene Rap1gap, encoding a RAP1 activation inhibitor, ameliorated podocyte injury resistance. Furthermore, injured podocytes in murine models of disease and kidney biopsies from glomerulosclerosis patients exhibited increased RAP1GAP, resulting in diminished glomerular RAP1 activation. In mouse models, podocyte-specific inactivation of Rap1a and Rap1b induced massive glomerulosclerosis and premature death. Podocyte-specific Rap1a and Rap1b haploinsufficiency also resulted in severe podocyte damage, including features of podocyte detachment. Over-expression of RAP1GAP in cultured podocytes induced loss of activated β1 integrin, which was similarly observed in kidney biopsies from patients. Furthermore, preventing elevation of RAP1GAP levels in injured podocytes maintained β1 integrin-mediated adhesion and prevented cellular detachment. Taken together, our findings suggest that increased podocyte expression of RAP1GAP contributes directly to podocyte dysfunction by a mechanism that involves loss of RAP1-mediated activation of β1 integrin.
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