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

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.

journal_name

J Dermatol Sci

authors

Lee CH,Hong CH,Chen YT,Chen YC,Shen MR

doi

10.1016/j.jdermsci.2012.06.004

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

173-80

issue

3

eissn

0923-1811

issn

1873-569X

pii

S0923-1811(12)00193-4

journal_volume

67

pub_type

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