title: Thrombomodulin regulates keratinocyte differentiation and promotes wound healing.
abstract: The membrane glycoprotein thrombomodulin (TM) has been implicated in keratinocyte differentiation and wound healing, but its specific function remains undetermined. The epidermis-specific TM knockout mice were generated to investigate the function of TM in these biological processes. Primary cultured keratinocytes obtained from TM(lox/lox); K5-Cre mice, in which TM expression was abrogated, underwent abnormal differentiation in response to calcium induction. Poor epidermal differentiation, as evidenced by downregulation of the terminal differentiation markers loricrin and filaggrin, was observed in TM(lox/lox); K5-Cre mice. Silencing TM expression in human epithelial cells impaired calcium-induced extracellular signal-regulated kinase pathway activation and subsequent keratinocyte differentiation. Compared with wild-type mice, the cell spreading area and wound closure rate were lower in keratinocytes from TM(lox/lox); K5-Cre mice. In addition, the lower density of neovascularization and smaller area of hyperproliferative epithelium contributed to slower wound healing in TM(lox/lox); K5-Cre mice than in wild-type mice. Local administration of recombinant TM (rTM) accelerated healing rates in the TM-null skin. These data suggest that TM has a critical role in skin differentiation and wound healing. Furthermore, rTM may hold therapeutic potential for the treatment of nonhealing chronic wounds.
authors: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors: Tsung-Lin
authors: TL
authors: Cheng
authors: Yu-Ting
authors: YT
authors: Wu
authors: Chao-Han
authors: CH
authors: Lai
authors: Yuan-Chung
authors: YC
authors: Kao
authors: Cheng-Hsiang
authors: CH
authors: Kuo
authors: Shu-Lin
authors: SL
authors: Liu
authors: Yun-Yan
authors: YY
authors: Hsu
authors: Po-Ku
authors: PK
authors: Chen
authors: Chia-Fong
authors: CF
authors: Cho
authors: Kuan-Chieh
authors: KC
authors: Wang
authors: Wei-Ling
authors: WL
authors: Lin
authors: Bi-Ing
authors: BI
authors: Chang
authors: Chun-Ming
authors: CM
authors: Chen
authors: Hartmut
authors: H
authors: Weiler
authors: Guey-Yueh
authors: GY
authors: Shi
authors: Hua-Lin
authors: HL
authors: Wu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D000091344:Filaggrin Proteins; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D061251:Primary Cell Culture; D018180:Thrombomodulin / Q000235:genetics* / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C569169:THBD protein, mouse; D018180:Thrombomodulin; D002118:Calcium