ArticleFibrogenesis & tissue repair2015
Human lung myofibroblast TGFβ1-dependent Smad2/3 signalling is Ca(2+)-dependent and regulated by KCa3.1 K(+) channels.
Article in Fibrogenesis & tissue repair, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Senicapoc in Patients with Idiopathic Pulmonary Fibrosis or Other Progressive Fibrotic Interstitial Lung Diseases: Protocol for a Randomised, Double-Blind, Placebo-Controlled, Multicentre Phase II Trial.Diagnostics (Basel, Switzerland) · 2026Article
- The cornea-trigeminal axis: potassium channels as master regulators of ocular surface homeostasis and sensory transduction.Frontiers in cell and developmental biology · 2026Review
- Polymer-Functionalized Mitochondrial Transplantation to Fibroblasts Counteracts a Pro-Fibrotic Phenotype.International journal of molecular sciences · 2023Article
- Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of CaLife (Basel, Switzerland) · 2022Article
- Atorvastatin and ezetimibe protect against hypercholesterolemia-induced lung oxidative stress, inflammation, and fibrosis in rats.Frontiers in medicine · 2022Article
- Evaluation of a novel combination of TRAM-34 and ascorbic acid for the treatment of corneal fibrosis in vivo.PloS one · 2022Article
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- Cell-Free Biological Approach for Corneal Stromal Wound Healing.Frontiers in pharmacology · 2021Review
- Evaluation of Pirfenidone and Nintedanib in a Human Lung Model of Fibrogenesis.Frontiers in pharmacology · 2021Article
- CaBritish journal of pharmacology · 2020Review
- The Role of KCNMB1 and BK Channels in Myofibroblast Differentiation and Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2020Article
- KScientific reports · 2019Article
- Hyperosmolar potassium inhibits myofibroblast conversion and reduces scar tissue formation.ACS biomaterials science & engineering · 2019Article
- GDF11 Modulates CaInternational journal of molecular sciences · 2018Article
- NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling.International journal of molecular medicine · 2018Article
- Blockade of KCa3.1: A novel target to treat TGF-β1 induced conjunctival fibrosis.Experimental eye research · 2018Article
- A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies in idiopathic pulmonary fibrosis.Scientific reports · 2018Article
- Article
- Oxidative stress promotes myocardial fibrosis by upregulating KPflugers Archiv : European journal of physiology · 2017Article
- Transcriptional and Post-Transcriptional Regulation of Thrombospondin-1 Expression: A Computational Model.PLoS computational biology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundIdiopathic pulmonary fibrosis (IPF) is a common and invariably lethal interstitial lung disease with poorly effective therapy. Blockade of the K(+) channel KCa3.1 reduces constitutive α-SMA and Smad2/3 nuclear translocation in IPF-derived human lung myofibroblasts (HLMFs), and inhibits several transforming growth factor beta 1 (TGFβ1)-dependent cell processes. We hypothesized that KCa3.1-dependent cell processes also regulate the TGFβ1-dependent Smad2/3 signalling pathway in HLMFs. HLMFs obtained from non-fibrotic controls (NFC) and IPF lungs were grown in vitro and examined for αSMA expression by immunofluorescence, RT-PCR, and flow cytometry. Two specific and distinct KCa3.1 blockers (TRAM-34 200 nM and ICA-17043 [Senicapoc] 100 nM) were used to determine their effects on TGFβ1-dependent signalling. Expression of phosphorylated and total Smad2/3 following TGFβ1 stimulation was determined by Western blot and Smad2/3 nuclear translocation by immunofluorescence.
resultsKCa3.1 block attenuated TGFβ1-dependent Smad2/3 phosphorylation and nuclear translocation, and this was mimicked by lowering the extracellular Ca(2+) concentration. KCa3.1 block also inhibited Smad2/3-dependent gene transcription (αSMA, collagen type I), inhibited KCa3.1 mRNA expression, and attenuated TGFβ1-dependent αSMA protein expression.
conclusionsKCa3.1 activity regulates TGFβ1-dependent effects in NFC- and IPF-derived primary HLMFs through the regulation of the TGFβ1/Smad signalling pathway, with promotion of downstream gene transcription and protein expression. KCa3.1 blockers may offer a novel approach to treating IPF.
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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.