title: The effect of p38MAPK on cyclic stretch in human facial hypertrophic scar fibroblast differentiation.
abstract: Hypertrophic scars (HTS), the excessive deposition of scar tissue by fibroblasts, is one of the most common skin disorders. Fibroblasts derived from surgical scar tissue produce high levels of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1). However, the molecular mechanisms for this phenomenon is poorly understood. Thus, the purpose of this study was to evaluate the molecular mechanisms of HTS and their potential therapeutic implications. Fibroblasts derived from skin HTS were cultured and characterized in vitro. The fibroblasts were synchronized and randomly assigned to two groups: cyclic stretch and cyclic stretch pre-treated with SB203580 (a p38MAPK inhibitor). Cyclic stretch at 10% strain was applied at a loading frequency of 10 cycles per minute (i.e. 5 seconds of tension and 5 seconds of relaxation) for 0 h, 6 h and 12 h. Cyclic stretch on HTS fibroblasts led to an increase in the expression of α-SMA and TGF-β1 mRNA and protein and the phosphorylation of p38MAPK. SB203580 reversed these effects and caused a decrease in matrix contraction. Furthermore, HTS fibroblast growth was partially blocked by p38MAPK inhibition. Therefore, the mechanism of cyclic stretch involves p38 MAPK, and its inhibition is suggested as a novel therapeutic strategy for HTS.
authors.affiliation: Department of Stomatology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, the People's Republic of China.
authors.forename: Qi-cui
authors.initials: QC
authors.lastname: Du
authors.forename: Dai-zun
authors.initials: DZ
authors.lastname: Zhang
authors.forename: Xiu-juan
authors.initials: XJ
authors.lastname: Chen
authors.forename: Gui
authors.initials: G
authors.lastname: Lan-Sun
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Wen-lin
authors.initials: WL
authors.lastname: Xiao
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology* / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580