ArticleJCI insight2019
Sonic hedgehog connects podocyte injury to mesangial activation and glomerulosclerosis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- m6A Modified VCAN Promotes Glomerular Endothelial Cells Injury and Diabetic Nephropathy by SHH Pathway.Applied biochemistry and biotechnology · 2026Article
- Article
- Extracellular vesicles play a central role in linking podocyte injury to mesangial activation in glomerular disease.Theranostics · 2025Article
- Myofibroblast-derived exosomes enhance macrophages to myofibroblasts transition and kidney fibrosis.Renal failure · 2024Article
- Proteome characterization of liver-kidney comorbidity after microbial sepsis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Central role of podocytes in mediating cellular cross talk in glomerular health and disease.American journal of physiology. Renal physiology · 2024Review
- Nox4-SH3YL1 complex is involved in diabetic nephropathy.iScience · 2024Article
- Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus nonciliated cells.Science advances · 2023Article
- Non-canonical Wnt/calcium signaling is protective against podocyte injury and glomerulosclerosis.Kidney international · 2022Article
- Smad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2022Review
- Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury.Molecular & cellular proteomics : MCP · 2020Article
- Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies.Frontiers in pharmacology · 2020Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Glomerular disease is characterized by proteinuria and glomerulosclerosis, two pathologic features caused by podocyte injury and mesangial cell activation, respectively. However, whether these two events are linked remains elusive. Here, we report that sonic hedgehog (Shh) is the mediator that connects podocyte damage to mesangial activation and glomerulosclerosis. Shh was induced in glomerular podocytes in various models of proteinuric chronic kidney diseases (CKD). However, mesangial cells in the glomeruli, but not podocytes, responded to hedgehog ligand. In vitro, Shh was induced in podocytes after injury and selectively promoted mesangial cell activation and proliferation. In a miniorgan culture of isolated glomeruli, Shh promoted mesangial activation but did not affect the integrity of podocytes. Podocyte-specific ablation of Shh in vivo exhibited no effect on proteinuria after adriamycin injection but hampered mesangial activation and glomerulosclerosis. Consistently, pharmacologic blockade of Shh signaling decoupled proteinuria from glomerulosclerosis. In humans, Shh was upregulated in glomerular podocytes in patients with CKD and its circulating level was associated with glomerulosclerosis but not proteinuria. These studies demonstrate that Shh mechanistically links podocyte injury to mesangial activation in the pathogenesis of glomerular diseases. Our findings also illustrate a crucial role for podocyte-mesangial communication in connecting proteinuria to glomerulosclerosis.
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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.