ArticleThe Journal of biological chemistry2013
Control of myofibroblast differentiation by microtubule dynamics through a regulated localization of mDia2.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Paclitaxel-induced cytoskeletal and focal adhesion reorganisation alters connexin43 and α-smooth muscle actin in cardiac cells.In vitro cellular & developmental biology. Animal · 2026Article
- Fenbendazole Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice via Suppression of Fibroblast-to-Myofibroblast Differentiation.International journal of molecular sciences · 2022Article
- Review
- Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review.Acta pharmacologica Sinica · 2022Review
- Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling.International journal of molecular sciences · 2022Review
- Immunomodulatory agents for COVID-19 treatment: possible mechanism of action and immunopathology features.Molecular and cellular biochemistry · 2022Review
- An open microfluidic coculture model of fibroblasts and eosinophils to investigate mechanisms of airway inflammation.Frontiers in bioengineering and biotechnology · 2022Article
- Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine.Journal of clinical medicine · 2021Review
- The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo.Biomedicines · 2021Article
- The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium.Life (Basel, Switzerland) · 2021Article
- Engrailed 1 coordinates cytoskeletal reorganization to induce myofibroblast differentiation.The Journal of experimental medicine · 2021Article
- Expression of serum response factor in the lung mesenchyme is essential for development of pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium.International journal of molecular sciences · 2021Article
- Article
- Efficacy of Colchicine and Budesonide in Improvement Outcomes of Patients with Coronavirus Infection 2019 in Damascus, Syria: A Randomized Control Trial.Interdisciplinary perspectives on infectious diseases · 2021Article
- The therapeutic potential of colchicine in the complications of COVID19. Could the immunometabolic properties of an old and cheap drug help?Metabolism open · 2020Article
- Interaction of microtubules and actin during the post-fusion phase of exocytosis.Scientific reports · 2019Article
- 5-Aryl-1,3,4-oxadiazol-2-ylthioalkanoic Acids: A Highly Potent New Class of Inhibitors of Rho/Myocardin-Related Transcription Factor (MRTF)/Serum Response Factor (SRF)-Mediated Gene Transcription as Potential Antifibrotic Agents for Scleroderma.Journal of medicinal chemistry · 2019Article
- Fibroblast growth factor 2 decreases bleomycin-induced pulmonary fibrosis and inhibits fibroblast collagen production and myofibroblast differentiation.The Journal of pathology · 2018Article
- Formin-dependent TGF-β signaling for epithelial to mesenchymal transition.Molecular biology of the cell · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Myofibroblast differentiation plays a critical role in wound healing and in the pathogenesis of fibrosis. We have previously shown that myofibroblast differentiation is mediated by the activity of serum response factor (SRF), which is tightly controlled by the actin polymerization state. In this study, we investigated the role of the microtubule cytoskeleton in modulating myofibroblast phenotype. Treatment of human lung fibroblasts with the microtubule-destabilizing agent, colchicine, resulted in a formation of numerous stress fibers and expression of myofibroblast differentiation marker proteins. These effects of colchicine were independent of Smad signaling but were mediated by Rho signaling and SRF, as they were attenuated by the Rho kinase inhibitor, Y27632, or by the SRF inhibitor, CCG-1423. TGF-β-induced myofibroblast differentiation was not accompanied by gross changes in the microtubule polymerization state. However, microtubule stabilization by paclitaxel attenuated TGF-β-induced myofibroblast differentiation. Paclitaxel had no effect on TGF-β-induced Smad activation and Smad-dependent gene transcription but inhibited actin polymerization, nuclear accumulation of megakaryoblastic leukemia-1 protein, and SRF activation. The microtubule-associated formin, mDIA2, localized to actin stress fibers upon treatment with TGF-β, and paclitaxel prevented this localization. Treatment with the formin inhibitor, SMI formin homology 2 domain, inhibited stress fiber formation and myofibroblast differentiation induced by TGF-β, without affecting Smad-phosphorylation or microtubule polymerization. Together, these data suggest that (a) TGF-β promotes association of mDia2 with actin stress fibers, which further drives stress fiber formation and myofibroblast differentiation, and (b) microtubule polymerization state controls myofibroblast differentiation through the regulation of mDia2 localization.
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Registered trials
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.