ArticleJournal of the American Society of Nephrology : JASN2014
Sonic hedgehog is a novel tubule-derived growth factor for interstitial fibroblasts after kidney injury.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 142 citations in OpenAlex.
- Mechanisms of regeneration and maladaptive repair in acute kidney injury.Nature reviews. Nephrology · 2026Review
- Perilipin 2 drives cisplatin-induced acute kidney injury in young but not aged kidneys.American journal of physiology. Renal physiology · 2026Article
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Emerging therapeutic pipelines on kidney fibrosis: challenges in translational research.Journal of translational medicine · 2026Review
- Critical role of transcription factor SOX4 in tubular epithelial cell dedifferentiation and fibroblast activation during kidney fibrosis.Kidney international · 2026Article
- Advances in the Targeted Drug Delivery System for Renal Fibrosis.International journal of nanomedicine · 2026Review
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- D-glucuronyl C5-Epimerase Binds to EGFR to Suppress Kidney Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular Basis of Oxidative Stress-Induced Acute Kidney Injury, Kidney Fibrosis, Chronic Kidney Disease, and Clinical Significance of Targeting Reactive Oxygen Species-Regulated Pathways to Treat Kidney Disease.Frontiers in bioscience (Scholar edition) · 2025Review
- Fibroblast activation and heterogeneity in fibrotic disease.Nature reviews. Nephrology · 2025Review
- Mechanisms of Acute Kidney Injury-Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities.Biomolecules · 2025Review
- The Kidney Precision Medicine Project and Single-Cell Biology of the Injured Proximal Tubule.The American journal of pathology · 2025Review
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Extracellular vesicles play a central role in linking podocyte injury to mesangial activation in glomerular disease.Theranostics · 2025Article
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Renal tubular epithelial cells response to injury in acute kidney injury.EBioMedicine · 2024Review
- Cell-cell communication in kidney fibrosis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis.Biological research · 2024Review
- Mitochondrial Signaling, the Mechanisms of AKI-to-CKD Transition and Potential Treatment Targets.International journal of molecular sciences · 2024Review
- Tubulointerstitial injury in proteinuric chronic kidney diseases.Frontiers in medicine · 2024Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Tubular epithelium constitutes the majority of the renal parenchyma and is the primary target of various kidney injuries. However, how the injured tubules drive interstitial fibroblast activation and proliferation remains poorly understood. Here, we investigated the role of sonic hedgehog (Shh), a secreted extracellular signaling protein, in fibroblast proliferation. Shh was induced in renal tubular epithelia in animal models of CKD induced by ischemia/reperfusion injury (IRI), adriamycin, or renal mass ablation, and in renal tubules of kidney biopsy specimens from CKD patients with different etiologies. Using Gli1-CreER(T2) reporter mice, we identified interstitial fibroblasts as the principal targets of renal Shh signaling in vivo. In vitro, incubation with Shh promoted normal rat kidney fibroblast proliferation, which was assessed by cell counting, MTT assay, and BrdU incorporation assay, and stimulated the induction of numerous proliferation-related genes. However, Shh had no effect on the proliferation of renal tubular epithelial cells. In vivo, overexpression of Shh promoted fibroblast expansion and aggravated kidney fibrotic lesions after IRI. Correspondingly, blockade of Shh signaling by cyclopamine, a small molecule inhibitor of Smoothened, inhibited fibroblast proliferation, reduced myofibroblast accumulation, and attenuated renal fibrosis. These studies identify Shh as a novel, specific, and potent tubule-derived growth factor that promotes interstitial fibroblast proliferation and activation. Our data also suggest that blockade of Shh signaling is a plausible strategy for therapeutic intervention of renal fibrosis.
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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.