title: 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.
  
  
  METHODS
  Using atomic force microscopy and confocal microscopy, we measured cellular rigidity and the expression of SMA in keloid fibroblasts treated with exogenous TGF-beta1.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Dermatology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chih-Hung
authors: CH
authors: Lee
authors: Chien-Hui
authors: CH
authors: Hong
authors: Ying-Ting
authors: YT
authors: Chen
authors: Yu-Chien
authors: YC
authors: Chen
authors: Meng-Ru
authors: MR
authors: Shen
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007627:Keloid / Q000378:metabolism*; D008297:Male; D018625:Microscopy, Atomic Force / Q000379:methods; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism*; D034622:RNA Interference; D013314:Stress, Mechanical; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000199:Actins; D053773:Transforming Growth Factor beta1