Upregulation of the Wnt/beta-catenin pathway induced by transforming growth factor-beta in hypertrophic scars and keloids.
Hypertrophic scars and keloids represent a dysregulated response to cutaneous wounds, which results in an excessive deposition of collagen. Transforming growth factor-beta (TGF-beta) is the key regulator in the pathogenesis of fibrosis. Accumulating evidence suggests that Wnt signalling and its effector beta-catenin also play an important role in wound healing. The role of Wnt/beta-catenin signalling in TGF-beta induced collagen deposition in hypertrophic scars and keloids was studied. Transcriptional assays and Western blotting was performed using fibroblast cell lines established from normal skin and hypertrophic scar tissue. Immunohistochemical studies were performed using scar tissues. We provide evidence that TGF-beta induces activation of beta-catenin mediated transcription in human dermal fibroblasts via the Smad3 and p38 MAPK pathways. Immunohistochemical studies demonstrated that beta-catenin protein levels are elevated in hypertrophic scar and keloid tissues. This finding may be relevant to the pathogenesis of hypertrophic scars and keloids.
Sato
Madoka
M
Department of Dermatology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. satomad@excite.co.jp
D000293:Adolescent; D015153:Blotting, Western; D002460:Cell Line; D002648:Child; D017439:Cicatrix, Hypertrophic / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007627:Keloid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*; D051153:Wnt Proteins / Q000378:metabolism*; D014945:Wound Healing; D051176:beta Catenin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051176:beta Catenin; D003094:Collagen; D048051:p38 Mitogen-Activated Protein Kinases