Thrombomodulin regulates keratinocyte differentiation and promotes wound healing

Tsung Lin Cheng, Yu Ting Wu, Chao Han Lai, Yuan Chung Kao, Cheng Hsiang Kuo, Shu Lin Liu, Yun Yan Hsu, Po Ku Chen, Chia Fong Cho, Kuan Chieh Wang, Wei Ling Lin, Bi Ing Chang, Chun Ming Chen, Hartmut Weiler, Guey Yueh Shi, Hua Lin Wu

研究成果: Article同行評審

20 引文 斯高帕斯(Scopus)

摘要

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 TMlox/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 TMlox/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 TMlox/lox; K5-Cre mice. In addition, the lower density of neovascularization and smaller area of hyperproliferative epithelium contributed to slower wound healing in TMlox/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.

原文English
頁(從 - 到)1638-1645
頁數8
期刊Journal of Investigative Dermatology
133
發行號6
DOIs
出版狀態Published - 2013 六月

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 皮膚科
  • 細胞生物學

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