title: Epithelial-mesenchymal transition in keloid tissues and TGF-β1-induced hair follicle outer root sheath keratinocytes.
abstract: Keloid is a skin fibrotic disease with the characteristics of recurrence and invasion, its pathogenesis still remains unrevealed. The epithelial-mesenchymal transition (EMT) is critical for wound healing, fibrosis, recurrence, and invasion of cancer. We sought to investigate the EMT in keloid and the mechanism through which the EMT regulates keloid formation. In keloid tissues, the expressions of EMT-associated markers and transforming growth factor (TGF)-β1/Smad3 signaling were examined by immunohistochemistry. In the keloid epidermis and dermal tissue, the expressions of genes related to the regulation of skin homeostasis, fibroblast growth factor receptor 2 (FGFR2) and p63, were analyzed using quantitative real-time polymerase chain reaction. The results showed that accompanying the loss of the epithelial marker E-cadherin and the gain of the mesenchymal markers fibroblast-specific protein 1 (FSP1) and vimentin in epithelial cells from epidermis and skin appendages, and in endothelial cells from dermal microvessels, enhanced TGF-β1 expression and Smad3 phosphorylation were noted in keloid tissues. Moreover, alternative splicing of the FGFR2 gene switched the predominantly expressed isoform from FGFR2-IIIb to -IIIc, concomitant with the decreased expression of ΔNp63 and TAp63, which changes might partially account for abnormal epidermis and appendages in keloids. In addition, we found that TGF-β1-induced hair follicle outer root sheath keratinocytes (ORSKs) and normal skin epithelial cells underwent EMT in vitro with ORSKs exhibiting more obvious EMT changes and more similar expression profiles for EMT-associated and skin homeostasis-related genes as in keloid tissues, suggesting that ORSKs might play crucial roles in the EMT in keloids. Our study provided insights into the molecular mechanisms mediating the EMT pathogenesis of keloids.
authors.affiliation: Research Center.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Research Center.
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.affiliation: Comprehensive Treatment Center of Scar.
authors.forename: Lianzhao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Plastic and Reconstructive Surgery.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Auricular Plastic and Reconstructive Surgery Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Ba-da-chu, Beijing, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pan
authors.affiliation: Research Center.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Research Center.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lv
authors.affiliation: Research Center.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhuang
authors.affiliation: Research Center.
authors.forename: Xuejian
authors.initials: X
authors.lastname: Sun
authors.affiliation: Research Center.
authors.forename: Ran
authors.initials: R
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007627:Keloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics*; D014945:Wound Healing / Q000235:genetics; D055815:Young Adult
chemical_list: D053773:Transforming Growth Factor beta1; D012313:RNA