Delayed skin wound repair in proline-rich protein tyrosine kinase 2 knockout mice
Document Type
Journal Article
Publication Date
3-7-2014
Journal
American journal of physiology. Cell physiology
Volume
306
Issue
10
DOI
10.1152/ajpcell.00331.2013
Keywords
epidermis; knockout mice; nonreceptor tyrosine kinase; proline-rich protein tyrosine kinase 2; wound healing
Abstract
Proline-rich protein tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family. We used Pyk2 knockout (Pyk2-KO) mice to study the role of Pyk2 in cutaneous wound repair. We report that the rate of wound closure was delayed in Pyk2-KO compared with control mice. To examine whether impaired wound healing of Pyk2-KO mice was caused by a keratinocyte cell-autonomous defect, the capacities of primary keratinocytes from Pyk2-KO and wild-type (WT) littermates to heal scratch wounds in vitro were compared. The rate of scratch wound repair was decreased in Pyk2-KO keratinocytes compared with WT cells. Moreover, cultured human epidermal keratinocytes overexpressing the dominant-negative mutant of Pyk2 failed to heal scratch wounds. Conversely, stimulation of Pyk2-dependent signaling via WT Pyk2 overexpression induced accelerated scratch wound closure and was associated with increased expression of matrix metalloproteinase (MMP)-1, MMP-9, and MMP-10. The Pyk2-stimulated increase in the rate of scratch wound repair was abolished by coexpression of the dominant-negative mutant of PKCδ and by GM-6001, a broad-spectrum inhibitor of MMP activity. These results suggest that Pyk2 is essential for skin wound reepithelialization in vivo and in vitro and that it regulates epidermal keratinocyte migration via a pathway that requires PKCδ and MMP functions.
APA Citation
Koppel, A. C., Kiss, A., Hindes, A., Burns, C. J., Marmer, B. L., Goldberg, G., Blumenberg, M., & Efimova, T. (2014). Delayed skin wound repair in proline-rich protein tyrosine kinase 2 knockout mice. American journal of physiology. Cell physiology, 306 (10). http://dx.doi.org/10.1152/ajpcell.00331.2013