ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2020
Myocardin and myocardin-related transcription factor-A synergistically mediate actin cytoskeletal-dependent inhibition of liver fibrogenesis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Actin cytoskeletal dynamics in hepatic myofibroblasts and fibrosis.Nature reviews. Gastroenterology & hepatology · 2026Review
- [Research progress on cellular senescence and liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Mechanosignaling via Integrins: Pivotal Players in Liver Fibrosis Progression and Therapy.Cells · 2025Review
- Identification of novel inhibitors of the transcriptional coactivator MRTF-A for HCC therapy.Molecular therapy. Oncology · 2024Article
- Review
- LAMB3 Promotes Myofibrogenesis and Cytoskeletal Reorganization in Endometrial Stromal Cells via the RhoA/ROCK1/MYL9 Pathway.Cell biochemistry and biophysics · 2024Article
- Signaling pathways that activate hepatic stellate cells during liver fibrosis.Frontiers in medicine · 2024Review
- Mechanobiology of portal hypertension.JHEP reports : innovation in hepatology · 2023Review
- MRTF-A gain-of-function in mice impairs homeostatic renewal of the intestinal epithelium.Cell death & disease · 2023Article
- Paxillin regulates liver fibrosis via actin polymerization and ERK activation in hepatic stellate cells.Journal of cell science · 2023Article
- Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis.Frontiers in molecular biosciences · 2023Review
- β-PIX cooperates with GIT1 to regulate endothelial nitric oxide synthase in sinusoidal endothelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Mechanical regulation of chromatin and transcription.Nature reviews. Genetics · 2022Review
- Mural Cell SRF Controls Pericyte Migration, Vessel Patterning and Blood Flow.Circulation research · 2022Article
- The cellular microenvironment and cytoskeletal actin dynamics in liver fibrogenesis.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2022Article
- O-GlcNAcylation inhibits hepatic stellate cell activation.Journal of gastroenterology and hepatology · 2021Article
- Review
Corrections and comments
- Erratum issuedCORRIGENDUM.2020
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Activation of hepatic stellate cells (HSCs), characterized by development of a robust actin cytoskeleton and expression of abundant extracellular matrix (ECM) proteins, such as type 1 collagen (COL.1), is a central cellular and molecular event in liver fibrosis. It has been demonstrated that HSCs express both myocardin and myocardin-related transcription factor-A (MRTF-A). However, the biological effects of myocardin and MRTF-A on HSC activation and liver fibrosis, as well as the molecular mechanism under the process, remain unclear. Here, we report that myocardin and MRTF-A's expression and nuclear accumulation are prominently increased during the HSC activation process, accompanied by robust activation of actin cytoskeleton dynamics. Targeting myocardin and MRTF-A binding and function with a novel small molecule, CCG-203971, led to dose-dependent inhibition of HSC actin cytoskeleton dynamics and abrogated multiple functional features of HSC activation (i.e., HSC contraction, migration and proliferation) and decreased COL.1 expression in vitro and liver fibrosis in vivo. Mechanistically, blocking the myocardin and MRTF-A nuclear translocation pathway with CCG-203971 directly inhibited myocardin/MRTF-A-mediated serum response factor (SRF), and Smad2/3 activation in the COL.1α2 promoter and indirectly abrogated actin cytoskeleton-dependent regulation of Smad2/3 and Erk1/2 phosphorylation and their nuclear accumulation. Finally, there was no effect of CCG-203971 on markers of inflammation, suggesting a direct effect of the compound on HSCs and liver fibrosis. These data reveal that myocardin and MRTF-A are two important cotranscriptional factors in HSCs and represent entirely novel therapeutic pathways that might be targeted to treat liver fibrosis.
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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 Socratic graph.