Fasudil inhibits actin polymerization and collagen synthesis and induces apoptosis in human urethral scar fibroblasts via the Rho/ROCK pathway
Received 4 November 2017
Accepted for publication 2 July 2018
Published 3 September 2018 Volume 2018:12 Pages 2707—2713
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Palas Chanda
Peer reviewer comments 3
Editor who approved publication: Professor Manfred Ogris
Xiao-Dong Li,* Yu-Peng Wu,* Shao-Hao Chen,* Ying-Chun Liang, Ting-Ting Lin, Tian Lin, Yong Wei, Xue-Yi Xue, Qing-Shui Zheng, Ning Xu
Departments of Urology, First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
*These authors contributed equally to this work
Purpose: To examine the effects and mechanism of action of fasudil on cytoskeletal polymerization, collagen synthesis, and apoptosis in fibroblasts derived from human urethral scar tissue.
Materials and methods: Fibroblasts treated with or without transforming growth factor β1 (TGF-β1, 10 ng/mL) were incubated with fasudil (12.5, 25, 50 µmol/L) for 24 hours. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of Arp2, Arp3, WASP, and WAVE2. Collagen I and III protein levels were also evaluated by Western blotting. The filamentous actin cytoskeleton was examined by immunofluorescence and epifluorescence microscopy. An Annexin V-FITC/PI staining assay was used to investigate apoptosis.
Results: TGF-β1-dependent induction of actin polymerization and collagen synthesis and promotion of apoptosis were dose dependent. When compared with untreated controls, fasudil significantly decreased the expression of Arp2, Arp3, WASP, WAVE2, Collagen I, and Collagen III in cells treated with or without TGF-β1. Fasudil also promoted apoptosis in cells, irrespective of TGF-β1 treatment.
Conclusion: Irrespective of TGF-β1 activation status, fasudil suppressed actin polymerization and collagen synthesis and induced apoptosis in human urethral scar fibroblasts via the Rho/ROCK signaling pathway.
Keywords: fasudil, polymerization, cytoskeleton, Rho/ROCK
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