ArticlePLoS biology2018
Jagged1/Notch2 controls kidney fibrosis via Tfam-mediated metabolic reprogramming.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 76 citations in OpenAlex.
- Mechanisms of regeneration and maladaptive repair in acute kidney injury.Nature reviews. Nephrology · 2026Review
- Massively parallel characterization and predictive modelling of neuronal regulatory variation.bioRxiv : the preprint server for biology · 2026Article
- Chromatin dynamics identifies 78 genes at loci associated with elevated intraocular pressure and primary open-angle glaucoma.bioRxiv : the preprint server for biology · 2026Article
- HNF4A P2 isoform alleviates kidney fibrosis by inhibiting dedifferentiation of proximal tubular cells through JAG1/NOTCH signaling.Cellular & molecular biology letters · 2026Article
- Dedifferentiated proximal tubular epithelial cells in diabetic kidney disease: pathogenic roles, repair potential, and therapeutic implications.Frontiers in endocrinology · 2026Review
- Simvastatin Mitigates Kidney Injury via Inhibition of the TNF-α/α-SMA Signaling Pathway in a Subtotal Nephrectomy Model.Journal of experimental pharmacology · 2026Article
- Lineage tracing reveals KSPFrontiers in cell and developmental biology · 2026Article
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- Fibroblast activation and heterogeneity in fibrotic disease.Nature reviews. Nephrology · 2025Review
- Notch2 Inhibition and Kidney Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2025Article
- Correcting mitochondrial loss mitigates NOTCH1-related aortopathy in mice.Nature cardiovascular research · 2025Article
- The role of notch signaling pathway in cancer: mechanistic insights, therapeutic potential, and clinical progress.Frontiers in immunology · 2025Review
- Role of miRNAs in macrophage-mediated kidney injury.Pediatric nephrology (Berlin, Germany) · 2024Review
- Metabolic reprogramming and renal fibrosis: what role might Chinese medicine play?Chinese medicine · 2024Review
- Hypermethylation leads to the loss of HOXA5, resulting in JAG1 expression and NOTCH signaling contributing to kidney fibrosis.Kidney international · 2024Article
- Article
- A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning.International journal of oral science · 2024Article
- miR-34c-5p inhibited fibroblast proliferation, differentiation and epithelial-mesenchymal transition in benign airway stenosis via MDMX/p53 pathway.Functional & integrative genomics · 2024Article
- Resveratrol prevents age-related heart impairment through inhibiting the Notch/NF-κB pathway.Food science & nutrition · 2024Article
- Modulation of Notch signaling pathway in activated hepatic stellate cells does not ameliorate the outcome of liver fibrosis in carbon tetrachloride and DDC-feeding models.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
While Notch signaling has been proposed to play a key role in fibrosis, the direct molecular pathways targeted by Notch signaling and the precise ligand and receptor pair that are responsible for kidney disease remain poorly defined. In this study, we found that JAG1 and NOTCH2 showed the strongest correlation with the degree of interstitial fibrosis in a genome-wide expression analysis of a large cohort of human kidney samples. Transcript analysis of mouse kidney disease models, including folic-acid (FA)-induced nephropathy, unilateral ureteral obstruction (UUO), or apolipoprotein L1 (APOL1)-associated kidney disease, indicated that Jag1 and Notch2 levels were higher in all analyzed kidney fibrosis models. Mice with tubule-specific deletion of Jag1 or Notch2 (Kspcre/Jag1flox/flox and Kspcre/Notch2flox/flox) had no kidney-specific alterations at baseline but showed protection from FA-induced kidney fibrosis. Tubule-specific genetic deletion of Notch1 and global knockout of Notch3 had no effect on fibrosis. In vitro chromatin immunoprecipitation experiments and genome-wide expression studies identified the mitochondrial transcription factor A (Tfam) as a direct Notch target. Re-expression of Tfam in tubule cells prevented Notch-induced metabolic and profibrotic reprogramming. Tubule-specific deletion of Tfam resulted in fibrosis. In summary, Jag1 and Notch2 play a key role in kidney fibrosis development by regulating Tfam expression and metabolic reprogramming.
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Registered trials
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