ArticlePloS one2023
The non-selective Rho-kinase inhibitors Y-27632 and Y-33075 decrease contraction but increase migration in murine and human hepatic stellate cells.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Estrogen receptor β activation attenuates portal hypertension and restores mesenteric vascular reactivity in cirrhotic ratsClinical and experimental hepatology · 2026Article
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
- Superior Antiproliferative and Enhanced Synergistic Effects of a ROCK Inhibitor in Multiple Models for Keloid Disease.JID innovations : skin science from molecules to population health · 2025Article
- miR-372-3p represses hepatic stellate cell activation via the RhoC/ROCK pathway.Cytotechnology · 2025Article
- ROCK2 Downregulation in Pediatric Medulloblastoma Increases Migration and Predicts the Involvement of SHH Non-canonical Signaling.The Yale journal of biology and medicine · 2025Article
- Rho-Associated Protein Kinase Activity Is Required for Tissue Homeostasis in theJournal of developmental biology · 2024Article
- Using human induced pluripotent stem cell-derived liver cells to investigate the mechanisms of liver fibrosis in vitro.Biochemical Society transactions · 2023Review
- Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis.Frontiers in molecular biosciences · 2023Review
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Rho-kinase ROCK II plays a major role in the activation of hepatic stellate cells (HSC), which are the key profibrotic and contractile cells contributing to the development of chronic liver disease. Inhibition of ROCK II ultimately blocks the phosphorylation of the myosin light chain (MLC) and thus inhibits stress fibre assembly and cell contraction. We investigated the effects of the ROCK inhibitors Y-33075 as well as Y-27632 in murine and human hepatic stellate cells.
methodsPrimary isolated HSC from FVB/NJ mice and the immortalized human HSC line TWNT-4 were culture-activated and incubated with Y-27632 and Y-33075 (10nM to 10μM) for 24h. Protein expression levels were analyzed by Western Blots and transcriptional levels of pro-fibrotic markers and proliferative markers were evaluated using real-time qPCR. Migration was investigated by wound-healing assay. Proliferation was assessed by BrdU assay. Contraction of HSC was measured using 3D collagen matrices after incubation with Y-27632 or Y-33075 in different doses.
resultsBoth Rho-kinase inhibitors, Y-27632 and Y-33075, reduced contraction, fibrogenesis and proliferation in activated primary mouse HSC (FVB/NJ) and human HSC line (TWNT-4) significantly. Y-33075 demonstrated a 10-times increased potency compared to Y-27632. Surprisingly, both inhibitors mediated a substantial and unexpected increase in migration of HSC in FVB/NJ.
conclusionROCK inhibition by the tested compounds decreased contraction but increased migration. Y-33075 proved more potent than Y27632 in the inhibition of contraction of HSCs and should be further evaluated in chronic liver disease.
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