Study Of Relationship Between The Characteristics Of Abnormal Proliferation And Differentiation Of Epithelial Cells And Different Outcomes Of Wound (Burn) Repair In Human Skin

Study on the characteristics of abnormalproliferation and differentiation of epithelial cells and different relations to outcomes of wound (burn) repair in human skin[Objective] Different patterns of repair, including normal scars, liypertrophic scars (HS), keloids (Ke), chronic ulcers and pseudoepitheliomatous hyperplasia (PEH), could result from healing of a wound. These pathological healing processes were not only associated with autoimmunity status, depth of local lesion, infection and inflammatory reaction, but also related to the main original mass of cells in the wound, such as epithelial cells and skin appendages (SAs). In this study, the effect of proliferation and differentiation of epithelial cells under physiological and pathological conditions on histogenesis and different repairing outcomes of repair was explored from those aspects including morphogenesis of embryonic epidermis and SAs, stratified epithelization of glandular epithelial cells in deep II burn wound (DBW), and the changes in epidermis and skin appendages during the course of HS, Ke and PEH formation, in order to elucidate the rule of wound healing and to provide a theoretical basis of promoting improvement in quality of wound healing.[Methods] Fetal skin of different embryonic ages, adult normal skin, wound tissues of DBW and SBW, tissues of healed skin wound, including HS, Ke and PEH. were collected from our hospital. The use of these samples was approved by the Committee of Scientific and Technology of 304th Hospital, Beijing, and signed consent of the involved patients. After morphological changes in epithelial tissue was observed with light and electron microscopy, the morphologic development of epidermal cells and skin appendages during human embryonic developmental stage, the relationship of the development of epithelial cells and differentiation during stratified epithelization of sweat gland in deep II degree burned wounds, and destruction of cells of appendages after pathological healing of wound, were explored with immunohistochemical method, immunofluorescent double labeling technology, mRNA in situ hybridization, flow cytometry analysis, and computer ancillary image scan and analysis. (1)The contents were as following: the relationship of proliferation and differentiation of epidermal cells with protein expression of various cytokeratins (CKs), such as labeling proteins of proliferativecells (CK5&6, CK14 and CK17), labeling molecules of epidermal stem cells (CK8&18 and CK19) and labeling proteins of terminal-differentiated cells (CK10), marking molecules of glandular epithelial cells (stem cell factor); (2) Effect of protein expression of matrix metalloproteinase (MMP)-2,-3,-9, Tissue inhibitor of matrix metalloproteinase (TIMP)-1,-2, IV-type collagen and laminin (LN) in epithelial cells on component formation of basement membrane. (3) Influence of expression levels of focal adhesion kinase (FAK), (CAM-1, E-cadherin (E-Cad) and B -catenin ( B -Cat) on abnormal differentiation and migration of epithelial cells.(4)The effect of the levels of expression of stem cell factor (SCF), its receptor (c-Kit/CD1 17 ) and interleukin (IL ) -6 on distribution, growth and differentiation of cells expressive CD14, CD68 and mast cell tryptase (MCT). (5) Correlationship of the expression of pan-cytokeratin (CKp), TGF-B1 and its receptor with the expression of Vim and a -SMA in epithelial cells underlying the effect of signal transduction mediated by transforming growth factor (TGF)-B1 / TGFBR I on epithelial- mesenchyrnal transformation epithelial-mesenchymal transformation (EMT) and mesenchymal-epithelial transformation (MET). (6)The relationship of protein expression and distribution of PCNA and apoptosis-related proteins (Bcl-2 and Bax) with proliferation and differentiation of epidermis, and epithelial cells in skin appendages.(7) Effect of signal transduction mediated by KGF2 and its receptor (FGFR2b/Bek) on proliferation and differentiation of embryonic epidermal cells and induction roles of skin appendage formation.Furtherm...