Open AccessNonmuscle Myosin II Activation Regulates Cell Proliferation, Cell Contraction, and Myofibroblast Differentiation in Keloid-Derived Fibroblasts
Author(s) -
Ying Lü,
Cheng Fang,
Chien Hui Hong,
Chieh Hsin Wu,
Yu Hung Lin,
Kee-Lung Chang,
Chih Hung Lee
Publication year - 2020
Publication title -
advances in wound care
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 24
eISSN - 2162-1934
pISSN - 2162-1918
DOI - 10.1089/wound.2019.0944
Subject(s) - keloid , myofibroblast , stress fiber , fibroblast , contractility , cell growth , myosin , microbiology and biotechnology , chemistry , cell , myosin light chain kinase , cancer research , signal transduction , pathology , biology , focal adhesion , medicine , endocrinology , fibrosis , biochemistry , in vitro
Objective: Keloid is an abnormal scar that often develops in high-tension skin. It is caused by excessive fibroblast proliferation and collagen deposition. Nonmuscle myosin IIA (NM-IIA) is an important motor protein that regulates the mechanical transduction of cells. However, the role of NM-IIA in keloid pathogenesis remains unclear. Approach: NM-IIA expression was examined and compared in keloid skin and normal skin by immunofluorescence. The organization of smooth muscle actin (SMA)-mediated stress fibers in normal and keloid fibroblasts (NFs and KFs, respectively) were determined. Cell proliferation and cell contractility were measured in fibroblasts derived from normal and keloids. The NM-II pharmacological inhibitor (blebbistatin) and RNA interference were applied to block NM-IIA and investigate its regulatory role in SMA-mediated stress fibers, cell contractility, and cell proliferation after NM-IIA inhibition. Results: NM-IIA expression is increased in keloid tissue. Inhibition of NM-II by blebbistatin or targeting NM-IIA by RNA interference reduced transforming growth factor beta (TGF-β)-mediated SMA-mediated stress fiber formation, cell proliferation, and cell contractility of NFs and KFs. Although TGF-β failed to mediate phosphorylation of myosin light chain (pMLC, the activator of NM-II), pMLC can interact with SMA-mediated stress fiber. Finally, inhibition of NM-II by blebbistatin also reduced NF and KF proliferation after TGF-β stimulation. Innovation: NM-IIA synergizes with TGF-β to regulate fibroblast proliferation, contraction activity, and myofibroblasts differentiation. Conclusion: NM-IIA might be one of the therapeutic targets in keloids.