ArticleAmerican journal of respiratory cell and molecular biology2018
The Rho Kinase Isoforms ROCK1 and ROCK2 Each Contribute to the Development of Experimental Pulmonary Fibrosis.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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67 citing papers in PubMed, 117 citations in OpenAlex.
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- RPE With ROCK-Mediated Epithelial-Mesenchymal Transition as a Key Contributor of Subretinal Fibrosis in AMD.Investigative ophthalmology & visual science · 2026Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Most Promising Emerging Therapies for Pulmonary Fibrosis: Targeting Novel Pathways.Biomedicines · 2026Review
- Natural therapeutics and traditional formulas targeting macrophage polarization in the fibrotic niche of idiopathic pulmonary fibrosis.Frontiers in immunology · 2026Review
- Transcriptome-Guided Drug Repurposing Identifies Homoharringtonine (HHT) as a Candidate for Radiation-Induced Pulmonary Fibrosis.Pharmaceutics · 2025Article
- Review
- Pulmonary Fibrosis-Focusing on the Future: Aspen Lung Conference 2024 Summary.American journal of respiratory cell and molecular biology · 2025Article
- Mechanosensing Pathways in the Progression of Pulmonary Fibrosis.Current opinion in biomedical engineering · 2025Article
- Combined treatment with mesenchymal stem cells and ROCK inhibitor Y-27632 ameliorates PMToxicology research · 2025Article
- DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case-control study.Scientific reports · 2025Article
- A small molecule PKCε inhibitor reduces hyperalgesia induced by paclitaxel or opioid withdrawal.JCI insight · 2025Article
- Evaluating Axatilimab as a treatment option for chronic graft-versus-host disease.Immunotherapy · 2025Review
- Review
- Tension-induced organelle stress: an emerging target in fibrosis.Trends in pharmacological sciences · 2025Review
- Mechanisms Regulating Mitochondrial Transfer in Human Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2024Article
- Y-27632 targeting ROCK1&2 modulates cell growth, fibrosis and epithelial-mesenchymal transition in hyperplastic prostate by inhibiting β-catenin pathway.Molecular biomedicine · 2024Article
- Paving the ROCKy Path to Novel Antifibrotics.American journal of respiratory cell and molecular biology · 2024Article
- Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.Nature reviews. Molecular cell biology · 2024Review
- Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.The Journal of clinical investigation · 2024Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Pulmonary fibrosis is thought to result from dysregulated wound repair after repetitive lung injury. Many cellular responses to injury involve rearrangements of the actin cytoskeleton mediated by the two isoforms of the Rho-associated coiled-coil-forming protein kinase (ROCK), ROCK1 and ROCK2. In addition, profibrotic mediators such as transforming growth factor-β, thrombin, and lysophosphatidic acid act through receptors that activate ROCK. Inhibition of ROCK activation may be a potent therapeutic strategy for human pulmonary fibrosis. Pharmacological inhibition of ROCK using nonselective ROCK inhibitors has been shown to prevent fibrosis in animal models; however, the specific roles of each ROCK isoform are poorly understood. Furthermore, the pleiotropic effects of this kinase have raised concerns about on-target adverse effects of ROCK inhibition such as hypotension. Selective inhibition of one isoform might be a better-tolerated strategy. In the present study, we used a genetic approach to determine the roles of ROCK1 and ROCK2 in a mouse model of bleomycin-induced pulmonary fibrosis. Using ROCK1- or ROCK2-haploinsufficient mice, we found that reduced expression of either ROCK1 or ROCK2 was sufficient to protect them from bleomycin-induced pulmonary fibrosis. In addition, we found that both isoforms contribute to the profibrotic responses of epithelial cells, endothelial cells, and fibroblasts. Interestingly, ROCK1- and ROCK2-haploinsufficient mice exhibited similar protection from bleomycin-induced vascular leak, myofibroblast differentiation, and fibrosis; however, ROCK1-haploinsufficient mice demonstrated greater attenuation of epithelial cell apoptosis. These findings suggest that selective inhibition of either ROCK isoform has the potential to be an effective therapeutic strategy for pulmonary fibrosis.
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