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Nonmuscle Myosin II Activation Regulates Cell Proliferation, Cell Contraction, and Myofibroblast Differentiation in Keloid-Derived Fibroblasts.

Advances in wound care (2020-09-18)
Ying-Yi Lu, Cheng-Chieh Fang, Chien-Hui Hong, Chieh-Hsin Wu, Yu-Hung Lin, Kee-Lung Chang, Chih-Hung Lee
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cell Counting Kit - 8, for quantitation of viable cell number in proliferation and cytotoxicity assays
Sigma-Aldrich
(Tyr[SO3H]27)Cholecystokinin fragment 26-33 Amide, ≥97% (HPLC), powder
Sigma-Aldrich
Anti-Myosin IIA, non muscle antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution