TGF-beta1 increases cell rigidity by enhancing expression of smooth muscle actin: Keloid-derived fibroblasts as a model for cellular mechanics

Chih Hung Lee, Chien Hui Hong, Ying Ting Chen, Yu Chien Chen, Meng-Ru Shen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Mechanical transduction contributes to appropriate cell functions. Clinically, keloid, an uncontrolled fibrous overgrowth and scarring, preferentially affects skin areas subject to higher mechanical tension than others. Keloid-derived fibroblasts have exaggerated TGF-beta1-mediated responses, including smooth muscle actin (SMA) expression, cellular contraction, and tissue remodeling, to mechanical strain compared to normal fibroblasts. Objective: This study asked if SMA contributes to cellular intrinsic rigidity using keloid -derived fibroblasts as a model. Method: Using atomic force microscopy and confocal microscopy, we measured cellular rigidity and the expression of SMA in keloid fibroblasts treated with exogenous TGF-beta1. Result: There was an increase of SMA expression in keloid tissue as well as keloid-derived fibroblasts. The cell rigidity increased by TGF-beta1 in keloid fibroblasts occurred concomitantly with increases in SMA expression. TGF-beta1 receptor 1 kinase inhibitors reduced TGF-beta1-induced cellular rigidity and SMA expression. Knocking down SMA with interference RNA resulted in a reduction of TGF-beta1-enhanced rigidity, suggesting that TGF-beta1 increases cell rigidity via SMA expression. Conclusion: We conclude that TGF-beta1 increases cell rigidity through TGF-beta1 receptor-SMA axis. This study reports that SMA, at least in part, contributes to cell rigidity in fibroblasts. SMA might be an appealing pharmaceutical target in keloids.

Original languageEnglish
Pages (from-to)173-180
Number of pages8
JournalJournal of Dermatological Science
Volume67
Issue number3
DOIs
Publication statusPublished - 2012 Sep 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

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