ArticleCell communication and signaling : CCS2019
Epithelial and interstitial Notch1 activity contributes to the myofibroblastic phenotype and fibrosis.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- The role of senescence in kidney ageing, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- LLLT-ADSCs Curtail the Progression of Keloid Through Exosomal miR-26a-5p Downregulating Jag/Notch Pathway.Lasers in surgery and medicine · 2026Article
- Midkine-Mediated Microglia Activation after Renal Injury Promotes Cognitive Impairment Following Ischemic Renal Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic depletion or pharmacological degradation of EZH2 attenuates renal fibrosis via suppressing Notch signaling.Clinical epigenetics · 2025Article
- Cross-species identification of conserved cell-type specific mechanisms during early placenta development in ruminants.Scientific reports · 2025Article
- Unravelling the reversion mechanisms of activated hepatic stellate cell properties by extracellular vesicles from mesenchymal stem cells.World journal of stem cells · 2025Review
- Fibroblast activation and heterogeneity in fibrotic disease.Nature reviews. Nephrology · 2025Review
- Endoplasmic reticulum stress aggravates ferroptosis via PERK/ATF4/HSPA5 pathway in UUO-induced renal fibrosis.Frontiers in pharmacology · 2025Article
- Biomimetic optimization of silicone breast implant integration: insights into wound healing and the foreign body response.Frontiers in bioengineering and biotechnology · 2025Review
- Inhibitory effects of herbal monomers on ferroptosis in renal fibrosis: a review and mechanistic study.Frontiers in pharmacology · 2025Review
- Lysosomal-Associated Protein Transmembrane 5, Tubular Senescence, and Progression of CKD.Journal of the American Society of Nephrology : JASN · 2024Article
- The Complex Interplay of TGF-β and Notch Signaling in the Pathogenesis of Fibrosis.International journal of molecular sciences · 2024Review
- The role of PI3K/Akt signaling pathway in chronic kidney disease.International urology and nephrology · 2024Review
- Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis.Journal of pharmaceutical analysis · 2024Review
- Molecular determinants of epithelial mesenchymal transition in mouse placenta and trophoblast stem cell.Scientific reports · 2023Article
- Huangqi decoction attenuates renal interstitial fibrosis transforming growth factor-β1/mitogen-activated protein kinase signaling pathways in 5/6 nephrectomy mice.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2022Article
- The anthelmintic drug niclosamide induces GSK-β-mediated β-catenin degradation to potentiate gemcitabine activity, reduce immune evasion ability and suppress pancreatic cancer progression.Cell death & disease · 2022Article
- Liproxstatin-1 attenuates unilateral ureteral obstruction-induced renal fibrosis by inhibiting renal tubular epithelial cells ferroptosis.Cell death & disease · 2021Article
- Inhibition of fibroblast growth factor-inducible 14 attenuates experimental tubulointerstitial fibrosis and profibrotic factor expression of proximal tubular epithelial cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNotch1 signalling is a stem-cell-related pathway that is essential for embryonic development, tissue regeneration and organogenesis. However, the role of Notch1 in the formation of myofibroblasts and fibrosis in kidneys following injury remains unknown.
methodsThe activity of Notch1 signalling was evaluated in fibrotic kidneys in CKD patients and in ureteral obstructive models in vivo and in cultured fibroblasts and TECs in vitro. In addition, the crosstalk of Notch1 with TGF-β1/Smad2/3 signalling was also investigated.
resultsNotch1 activity was elevated in fibrotic kidneys of rat models and patients with chronic kidney disease (CKD). Further study revealed that epithelial and interstitial Notch1 activity correlated with an α-SMA-positive myofibroblastic phenotype. In vitro, injury stimulated epithelial Notch1 activation and epithelial-mesenchymal transition (EMT), resulting in matrix deposition in tubular epithelial cells (TECs). Additionally, interstitial Notch1 activation in association with fibroblast-myofibroblast differentiation (FMD) in fibroblasts mediated a myofibroblastic phenotype. These TGF-β1/Smad2/3-dependent phenotypic transitions were abolished by Notch1 knockdown or a specific antagonist, DAPT, and were exacerbated by Notch1 overexpression or an activator Jagged-1-Fc chimaera protein. Interestingly, as a major driving force behind the EMT and FMD, TGF-β1, also induced epithelial and interstitial Notch1 activity, indicating that TGF-β1 may engage in crosstalk with Notch1 signalling to trigger fibrogenesis.
conclusionThese findings suggest that epithelial and interstitial Notch1 activation in kidneys following injury contributes to the myofibroblastic phenotype and fibrosis through the EMT in TECs and to the FMD in fibroblasts by targeting downstream TGF-β1/Smad2/3 signalling.
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