ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Mechanism of fibrotic cardiomyopathy in mice expressing truncated Rho-associated coiled-coil protein kinase 1.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- RhoGEF Ect2 supports RhoA activity at cell-cell junctions through desmoplakin.Life science alliance · 2026Article
- First-in-human study of CPL'116 - a dual JAK/ROCK inhibitor - in healthy subjects.Frontiers in pharmacology · 2025Article
- ROCK1 deficiency preserves caveolar compartmentalization of signaling molecules and cell membrane integrity.FASEB bioAdvances · 2024Article
- SLIT3 promotes cardiac fibrosis and differentiation of cardiac fibroblasts by RhoA/ROCK1 signaling pathway.Iranian journal of basic medical sciences · 2024Article
- Rho Kinases in Embryonic Development and Stem Cell Research.Archivum immunologiae et therapiae experimentalis · 2022Review
- Transcription Factors Involved in the Development and Prognosis of Cardiac Remodeling.Frontiers in pharmacology · 2022Review
- IGF-1 protects against angiotensin II-induced cardiac fibrosis by targeting αSMA.Cell death & disease · 2021Article
- ROCK (RhoA/Rho Kinase) in Cardiovascular-Renal Pathophysiology: A Review of New Advancements.Journal of clinical medicine · 2020Review
- HaploinsufficientCells · 2020Article
- Discovery of vascular Rho kinase (ROCK) inhibitory peptides.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Disruption of both ROCK1 and ROCK2 genes in cardiomyocytes promotes autophagy and reduces cardiac fibrosis during aging.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Rho kinase signaling and cardiac physiology.Current opinion in physiology · 2018Article
- Effects of Total Flavone fromEvidence-based complementary and alternative medicine : eCAM · 2017Article
- Rho Kinases and Cardiac Remodeling.Circulation journal : official journal of the Japanese Circulation Society · 2016Review
- Rnd3/RhoE Modulates Hypoxia-Inducible Factor 1α/Vascular Endothelial Growth Factor Signaling by Stabilizing Hypoxia-Inducible Factor 1α and Regulates Responsive Cardiac Angiogenesis.Hypertension (Dallas, Tex. : 1979) · 2016Article
- Signaling Pathways in Cardiac Myocyte Apoptosis.BioMed research international · 2016Review
- Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity.Cancer medicine · 2015Article
- ROCK and Rho: Promising therapeutic targets to ameliorate pulmonary fibrosis.The American journal of pathology · 2015Article
- The Function of Rho-Associated Kinases ROCK1 and ROCK2 in the Pathogenesis of Cardiovascular Disease.Frontiers in pharmacology · 2015Review
- RhoA signaling in cardiomyocytes protects against stress-induced heart failure but facilitates cardiac fibrosis.Science signaling · 2014Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
We have previously found that in failing human hearts, Rho-associated coiled-coil protein kinase 1 (ROCK1) is processed by caspase-3 into an active isoform, ROCKΔ1. The purpose of the current investigation was to elucidate the pathological consequences of truncated ROCK1 accumulation in the heart, the associated molecular mechanism of ROCKΔ1-mediated cardiac phenotype, and the molecular signaling between Rho kinase activation in cardiomyocytes and extracellular matrix response. We generated transgenic mice expressing ROCKΔ1 in cardiomyocytes to mimic the situation observed in human heart disease, whereas an additional kinase-deficient mouse was generated as a control. The ROCKΔ1 transgenic mice developed fibrotic cardiomyopathy with diastolic dysfunction. Transgenic hearts displayed activated TGFβ1 and NF-κB signaling and a release of a subset of cytokines and were susceptible to angiotensin II stress. Treatment with a Rho kinase inhibitor attenuated the fibrotic phenotype. Cardiac fibroblasts differentiated into myofibroblasts when cocultured with transgenic cardiomyocytes but not with wild-type cardiomyocytes. Inhibitors of Rho kinase as well as TGFβR1 and NF-κB decreased these effects. The serum response factor-dependent TGFβ1 regulation was shown to be responsible for the Rho kinase-mediated activation of TGFβ1 signaling. We conclude that ROCKΔ1 is a novel fibrotic factor. Activation of TGFβ1 and NF-κB signaling contributes to the Rho kinase-mediated pathological fibrosis.
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