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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1638-1645
Number of pages8
JournalJournal of Investigative Dermatology
Volume133
Issue number6
DOIs
Publication statusPublished - 2013 Jun

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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  • Cite this

    Cheng, T. L., Wu, Y. T., Lai, C. H., Kao, Y. C., Kuo, C. H., Liu, S. L., Hsu, Y. Y., Chen, P. K., Cho, C. F., Wang, K. C., Lin, W. L., Chang, B. I., Chen, C. M., Weiler, H., Shi, G. Y., & Wu, H. L. (2013). Thrombomodulin regulates keratinocyte differentiation and promotes wound healing. Journal of Investigative Dermatology, 133(6), 1638-1645. https://doi.org/10.1038/jid.2013.8