title: Abnormalities in the basement membrane structure promote basal keratinocytes in the epidermis of hypertrophic scars to adopt a proliferative phenotype.
abstract: The majority of studies on scar formation have mainly focused on the dermis and little is known of the involvement of the epidermis. Previous research has demonstrated that the scar tissue-derived keratinocytes are different from normal cells at both the genetic and cell biological levels; however, the mechanisms responsible for the fundamental abnormalities in keratinocytes during scar development remain elusive. For this purpose, in this study, we used normal, wound edge and hypertrophic scar tissue to examine the morphological changes which occur during epidermal regeneration as part of the wound healing process and found that the histological structure of hypertrophic scar tissues differed from that of normal skin, with a signiﬁcant increase in epidermal thickness. Notably, staining of the basement membrane (BM) appeared to be absent in the scar tissues. Moreover, immunofluorescence staining for cytokeratin (CK)10, CK14, CK5, CK19 and integrin-β1 indicated the differential expression of cell markers in the epidermal keratinocytes among the normal, wound edge and hypertrophic scar tissues, which corresponded with the altered BM structures. By using a panel of proteins associated with BM components, we validated our hypothesis that the BM plays a significant role in regulating the cell fate decision of epidermal keratinocytes during skin wound healing. Alterations in the structure of the BM promote basal keratinocytes to adopt a proliferative phenotype both in vivo and in vitro.
authors.affiliation: Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Trauma Center of Postgraduate Medical School, Chinese PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Yang
authors.affiliation: Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, The First Affiliated Hospital to the Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Yexiao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, The First Affiliated Hospital to the Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Geng
authors.affiliation: Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, The First Affiliated Hospital to the Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Ma
authors.affiliation: Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Trauma Center of Postgraduate Medical School, Chinese PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Trauma Center of Postgraduate Medical School, Chinese PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
mesh_terms: D000293:Adolescent; D000328:Adult; D001485:Basement Membrane / Q000473:pathology*; D015415:Biomarkers; D002454:Cell Differentiation; D017439:Cicatrix, Hypertrophic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D008297:Male; D010641:Phenotype; D014945:Wound Healing; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007633:Keratins