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• W1509716601 abstract "1. Hyperglycaemia promotes the proliferation of cardiac fibroblasts (CFs) and collagen synthesis in CFs. The objectives of the present study were to determine the effects of fasudil hydrochloride hydrate, a Rho-kinase (ROCK) inhibitor, on high glucose (HG)-induced proliferation of CFs and collagen production in rat CFs and to investigate the molecular mechanism of action of fasudil. 2. Rat CFs were cultured in Dulbecco's modified Eagle's medium, supplemented with 5.5 or 25 mmol/L d-glucose or 5.5 mmol/L d-glucose + 19.5 mmol/L mannose, in the presence of absence of fasudil (50 or 100 μmol/L). Proliferation was measured by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, whereas the production of Type I collagen was evaluated using ELISA and the expression of ROCK1, c-Jun N-terminal kinase (JNK) and Type I procollagen mRNA was determined by reverse transcription-polymerase chain reaction. Intracellular Type I procollagen protein levels were evaluated using immunocytochemistry. Western blot analysis was used to evaluate the phosphorylation of myosin phosphatase target subunit 1 (MYPT1), JNK and Smad2/3, as well as c-jun protein levels. 3. Both concentrations of fasudil effectively inhibited HG (25 mmol/L d-glucose)-induced increases in the proliferation of CFs and collagen synthesis, concomitant with suppression of HG-induced upregulation of ROCK1 and JNK mRNA expression and c-jun protein levels, as well as the phosphorylation of MYPT1, JNK and Smad2/3. 4. These data suggest that ROCK activation is essential for the proliferation of CFs and collagen synthesis induced by HG. Fasudil suppressed HG-induced increases in the proliferation of CFs and collagen synthesis, which may be associated with inhibition of the JNK and transforming growth factor β/Smad pathways. The results of the present study indicate that inhibition of ROCK may be a novel therapeutic target for the prevention of diabetic cardiac fibrosis." @default.
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• W1509716601 date "2011-05-23" @default.
• W1509716601 modified "2023-09-25" @default.
• W1509716601 title "Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, suppresses high glucose-induced proliferation and collagen synthesis in rat cardiac fibroblasts" @default.
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• W1509716601 doi "https://doi.org/10.1111/j.1440-1681.2011.05523.x" @default.
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