ArticleInternational urology and nephrology2022
Verapamil inhibited the development of ureteral stricture by blocking CaMK II-mediated STAT3 and Smad3/JunD pathways.
Article in International urology and nephrology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 9 citations in OpenAlex.
- TGF-β1 induces epithelial-mesenchymal transition and fibrosis of ureteral epithelial cells via targeting RACK1 in ureteropelvic junction obstruction.Translational pediatrics · 2026Article
- CaMKII phosphorylation promotes renal fibrosis in cisplatin induced chronic kidney disease via Smad 2/3 activation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Verapamil Reduces Collagen Synthesis to Alleviate Ureteral Scar Formation by Inhibiting KDM1A-Mediated Epigenetic Silencing of SESN2.Kidney & blood pressure research · 2026Article
- Computational modelling of cardiac fibroblast signalling reveals a key role for CaThe Journal of physiology · 2025Article
- Saliva-derived extracellular vesicles: a promising therapeutic approach for salivary gland fibrosis.Journal of translational medicine · 2025Article
- Examining the NEUROG2 lineage and associated gene expression in human cortical organoids.Development (Cambridge, England) · 2025Article
- Verapamil inhibits inflammation and promotes autophagy to alleviate ureteral scar by regulation of CaMK IIδ/STAT3 axis.Renal failure · 2024Article
- Glucose fluctuations aggravate myocardial fibrosis via activating the CaMKII/Stat3 signaling in type 2 diabtetes.Diabetology & metabolic syndrome · 2023Article
- Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation.International journal of molecular sciences · 2023Review
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9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundUreteral stricture (US) is a fibrotic process that leads to urinary tract obstruction and even kidney damage, with the characteristic of reduced extracellular matrix (ECM) degradation and increased collagen synthesis. Verapamil, as a calcium channel blocker, was reported to prevent scar formation. Our work aimed to investigate the biological effects and mechanism of verapamil in US.
methodsFibroblasts were subjected to transforming growth factor-beta 1 (TGF-β1) to stimulate collagen synthesis, and the messenger ribonucleic acid (mRNA) and protein expressions in fibroblasts were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The location of phosphorylation-signal transducer and activator of transcription 3 (p-STAT3) and Jund proto-oncogene subunit (JunD) in fibroblasts were determined by immunofluorescence (IF). The binding relationship between signal transducer and activator of transcription 3 (STAT3) and collagen type I alpha1 (COL1A1)/collagen type III alpha 1 chain (COL3A1) and the binding relationship between JunD and tissue inhibitor of metalloproteinases-1 (TIMP-1) were verified by dual luciferase reporter gene and chromatin Immunoprecipitation (ChIP) assays.
resultsHerein, we found that verapamil could inhibit TGF-β1/Ca2 + ⁄calmodulin-dependent protein kinase II (CaMK II)-mediated STAT3 activation in fibroblasts, and STAT3 inhibition repressed collagen production. In addition, verapamil could inhibit TGF-β1/CaMK II-mediated Mothers against DPP homolog 3 (Smad3)/JunD pathway activation in fibroblasts, and JunD silencing inhibited TIMP1 (a matrix metalloproteinase inhibitor) expression. Our subsequent experiments revealed that STAT3 bound with COL1A1 promoter and COL3A1 promoter and activated their transcription, and JunD bound with TIMP1 promoter and activated its transcription. Moreover, as expected, STAT3 activation could eliminate the inhibitory effect of verapamil treatment on TGF-β1-induced collagen production in fibroblasts, and JunD overexpression reversed the inhibitory effect of verapamil treatment on TGF-β1-induced TIMP1 expression in fibroblasts.
conclusionVerapamil inhibited collagen production and TIMP-1 expression in US by blocking CaMK II-mediated STAT3 and Smad3/JunD pathways.
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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 Socratic graph.