ArticleInflammatory bowel diseases2014
Novel Rho/MRTF/SRF inhibitors block matrix-stiffness and TGF-β-induced fibrogenesis in human colonic myofibroblasts.
Article in Inflammatory bowel diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 195 citations in OpenAlex.
- Systematic Analysis of MRTFB Phosphoproteomic Datasets Reveals Co-Regulated Kinase Networks and Co-Occurring Phosphosites Associated with the Actin Cytoskeleton Pathway.Current issues in molecular biology · 2026Article
- Branched-chain amino acid transaminase 1-mediated pathway promotes proline-dependent collagen production in cardiac myofibroblasts.The Journal of clinical investigation · 2026Article
- 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
- Suppression of the myofibroblastic cancer-associated fibroblast phenotype to enhance anti-PD-1 response.Journal of experimental & clinical cancer research : CR · 2026Article
- Phenotype-driven management in ileocecal Crohn's disease: a narrative review with a proposed research framework.Therapeutic advances in gastroenterology · 2026Review
- Developing a protocol to counteract spontaneous in vitro activation of intestinal fibroblasts using design of experiments.npj biomedical innovations · 2026Article
- LncRNANon-coding RNA research · 2025Article
- Developing a Cell Culture Protocol to Induce Quiescence in Intestinal Fibroblasts Using Design of Experiments Statistical Optimization.Research square · 2025Article
- Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin-Related Transcription Factor-A.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Mechanism of SC targeting RhoA regulation and its potential value in gastric cancer therapy.Biochemistry and biophysics reports · 2025Article
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Fibrosis: cross-organ biology and pathways to development of innovative drugs.Nature reviews. Drug discovery · 2025Review
- Changes in Gene Expression Patterns in Young and Senescent Fibroblasts in Glycated Three-Dimensional Collagen Matrices.International journal of molecular sciences · 2025Article
- The Pathogenesis of Inflammatory Bowel Diseases.The Surgical clinics of North America · 2025Review
- Matrix stiffness regulates nucleus pulposus cell glycolysis by MRTF-A-dependent mechanotransduction.Bone research · 2025Article
- Mechanosignaling via Integrins: Pivotal Players in Liver Fibrosis Progression and Therapy.Cells · 2025Review
- Tension-induced organelle stress: an emerging target in fibrosis.Trends in pharmacological sciences · 2025Review
- Aging and Intestinal Fibrosis: Mechanisms, Implications, and Therapeutic Strategies.Clinical interventions in aging · 2025Review
- New insights into the pharmacological inhibition of SRF activity: Key inhibitory targets and mechanisms.Vascular pharmacology · 2024Review
- Microprotein-encoding RNA regulation in cells treated with pro-inflammatory and pro-fibrotic stimuli.BMC genomics · 2024Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRas homolog gene family, member A (RhoA)/Rho-associated coiled-coil forming protein kinase signaling is a key pathway in multiple types of solid organ fibrosis, including intestinal fibrosis. However, the pleiotropic effects of RhoA/Rho-associated coiled-coil forming protein kinase signaling have frustrated targeted drug discovery efforts. Recent recognition of the role of Rho-regulated gene transcription by serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factor A (MRTF-A) suggest a novel locus for pharmacological intervention.
methodsBecause RhoA signaling is mediated by both physical and biochemical stimuli, we examined whether pharmacological inhibition of RhoA or the downstream transcription pathway of MRTF-A/SRF could block intestinal fibrogenesis in 2 in vitro models.
resultsIn this study, we demonstrate that inhibition of RhoA signaling blocks both matrix-stiffness and transforming growth factor beta-induced fibrogenesis in human colonic myofibroblasts. Repression of alpha-smooth muscle actin and collagen expression was associated with the inhibition of MRTF-A nuclear localization. CCG-1423, a first-generation Rho/MRTF/SRF pathway inhibitor, repressed fibrogenesis in both models, yet has unacceptable cytotoxicity. Novel second-generation inhibitors (CCG-100602 and CCG-203971) repressed both matrix-stiffness and transforming growth factor beta-mediated fibrogenesis as determined by protein and gene expression in a dose-dependent manner.
conclusionsTargeting the Rho/MRTF/SRF mechanism with second-generation Rho/MRTF/SRF inhibitors may represent a novel approach to antifibrotic therapeutics.
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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.