title: Wnt/β-catenin pathway forms a negative feedback loop during TGF-β1 induced human normal skin fibroblast-to-myofibroblast transition.
abstract: BACKGROUND
  Fibroblast-to-myofibroblast transition is a key event during wound healing and hypertrophic scar formation. Previous studies suggested Wnt/β-catenin signaling might be involved in the wound healing. However, its specific role in skin fibroblast-to-myofibroblast transition remains unclear.
  
  
  OBJECTIVE
  To investigate the specific role of β-catenin during the transforming growth factor-β1 induced normal skin myofibroblasts transition.
  
  
  METHODS
  By real-time quantitative polymerase chain reaction, Western-blot and immunocytochemistry, the activation of Wnt/β-catenin pathway in cultured human normal skin fibroblasts during TGF-β1 induced fibroblast-to-myofibroblast transition was investigated. The effects of β-catenin on myofibroblasts transition were also investigated when SB-216763, over-expression and siRNA of β-catenin were utilized. In addition, fibroblasts populated collagen lattices contraction assays were conducted to examine the effects of β-catenin on the contractility of the fibroblasts induced by TGF-β1. Furthermore, the effects of β-catenin on the expression of α-smooth muscle actin and collagen types I and III in hypertrophic scar derived fibroblasts were studied.
  
  
  RESULTS
  The expression of Wnts mRNA and β-catenin protein was up-regulated by TGF-β1 stimulation during the myofibroblasts transition. Both of SB-216763 and β-catenin over-expression was paralleled with decreased expression of α-smooth muscle actin, collagen types I and III, while siRNA targeting β-catenin leads to up-regulation of α-smooth muscle actin, collagen types I and III. The increased contractility and α-smooth muscle actin expression of the fibroblasts in the collagen lattices induced by TGF-β1 was inhibited by SB-216763. In addition, the expression levels of α-smooth muscle actin, collagen types I and III in hypertrophic scar derived fibroblasts were also down-regulated by SB-216763.
  
  
  CONCLUSIONS
  Specifically in normal skin fibroblasts, β-catenin might be involved in the myofibroblasts transition and negatively regulate the TGF-β1-induced myofibroblast transition.
authors: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi 710032, China.
authors: Jiaqi
authors: J
authors: Liu
authors: Yunchuan
authors: Y
authors: Wang
authors: Qing
authors: Q
authors: Pan
authors: Yingjun
authors: Y
authors: Su
authors: Zhanfeng
authors: Z
authors: Zhang
authors: Juntao
authors: J
authors: Han
authors: Xiongxiang
authors: X
authors: Zhu
authors: Chaowu
authors: C
authors: Tang
authors: Dahai
authors: D
authors: Hu
mesh_terms: D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D058628:Myofibroblasts / Q000166:cytology*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism*; D014945:Wound Healing; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin