ArticleAmerican journal of physiology. Lung cellular and molecular physiology2011
Delayed stress fiber formation mediates pulmonary myofibroblast differentiation in response to TGF-β.
Article in American journal of physiology. Lung cellular and molecular physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 111 citations in OpenAlex.
- TGF-β1 expression in chromophobe renal cell carcinoma and renal oncocytoma.European journal of histochemistry : EJH · 2014Trial
- Roflumilast Inhibits Fibrogenic Activation in Human Intestinal Myofibroblasts via Inhibition of Myocardin-Related Transcription Factor/Serum Response Factor Signaling.International journal of molecular sciences · 2026Article
- An agent-based model suggests how senescent cell behavior and matrix mechanics drive pulmonary fibrosis in aged mice.bioRxiv : the preprint server for biology · 2026Article
- Gα12 and Gα13 proteins are required for transforming growth factor-β-induced myofibroblast differentiation.The Biochemical journal · 2024Article
- Vascular fibrosis and extracellular matrix remodelling in post-COVID 19 conditions.Infectious medicine · 2024Review
- Critical role of Gα12 and Gα13 proteins in TGF-β-induced myofibroblast differentiation.bioRxiv : the preprint server for biology · 2024Article
- In Vitro Mechanical Stimulation to Reproduce the Pathological Hallmarks of Human Cardiac Fibrosis on a Beating Chip and Predict The Efficacy of Drugs and Advanced Therapies.Advanced healthcare materials · 2024Article
- Logic-based mechanistic machine learning on high-content images reveals how drugs differentially regulate cardiac fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Anoctamin-1 is induced by TGF-β and contributes to lung myofibroblast differentiation.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Anoctamin-1 is induced by TGF-beta and contributes to lung myofibroblast differentiation.bioRxiv : the preprint server for biology · 2023Article
- Logic-based mechanistic machine learning on high-content images reveals how drugs differentially regulate cardiac fibroblasts.bioRxiv : the preprint server for biology · 2023Article
- Rhinovirus induces airway remodeling: what are the physiological consequences?Respiratory research · 2023Review
- Nestin and Notch3 collaboratively regulate angiogenesis, collagen production, and endothelial-mesenchymal transition in lung endothelial cells.Cell communication and signaling : CCS · 2023Article
- Cross talk between lysine methyltransferase Smyd2 and TGF-β-Smad3 signaling promotes renal fibrosis in autosomal dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2022Article
- Extracellular matrix dynamics: tracking in biological systems and their implications.Journal of biological engineering · 2022Review
- Single-Cell Transcriptomic Analysis Reveals a Hepatic Stellate Cell-Activation Roadmap and Myofibroblast Origin During Liver Fibrosis in Mice.Hepatology (Baltimore, Md.) · 2021Article
- Ventral stress fibers induce plasma membrane deformation in human fibroblasts.Molecular biology of the cell · 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
- Corneal myofibroblasts and fibrosis.Experimental eye research · 2020Review
- Protein diaphanous homolog 1 (Diaph1) promotes myofibroblastic activation of hepatic stellate cells by regulating Rab5a activity and TGFβ receptor endocytosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Myofibroblast differentiation induced by transforming growth factor-β (TGF-β) and characterized by de novo expression of smooth muscle (SM)-specific proteins is a key process in wound healing and in the pathogenesis of fibrosis. We have previously shown that TGF-β-induced expression and activation of serum response factor (SRF) is required for this process. In this study, we examined the signaling mechanism for SRF activation by TGF-β as it relates to pulmonary myofibroblast differentiation. TGF-β stimulated a profound, but delayed (18-24 h), activation of Rho kinase and formation of actin stress fibers, which paralleled SM α-actin expression. The translational inhibitor cycloheximide blocked these processes without affecting Smad-dependent gene transcription. Inhibition of Rho kinase by Y-27632 or depolymerization of actin by latrunculin B resulted in inhibition TGF-β-induced SRF activation and SM α-actin expression, having no effect on Smad signaling. Conversely, stabilization of actin stress fibers by jasplakinolide was sufficient to drive these processes in the absence of TGF-β. TGF-β promoted a delayed nuclear accumulation of the SRF coactivator megakaryoblastic leukemia-1 (MKL1)/myocardin-related transcription factor-A, which was inhibited by latrunculin B. Furthermore, TGF-β also induced MKL1 expression, which was inhibited by latrunculin B, by SRF inhibitor CCG-1423, or by SRF knockdown. Together, these data suggest a triphasic model for myofibroblast differentiation in response to TGF-β that involves 1) initial Smad-dependent expression of intermediate signaling molecules driving Rho activation and stress fiber formation, 2) nuclear accumulation of MKL1 and activation of SRF as a result of actin polymerization, and 3) SRF-dependent expression of MKL1, driving further myofibroblast differentiation.
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Registered trials
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