Delayed skin wound repair in proline-rich protein tyrosine kinase 2 knockout mice
| العنوان: | Delayed skin wound repair in proline-rich protein tyrosine kinase 2 knockout mice |
|---|---|
| المؤلفون: | Anna Hindes, Carole J. Burns, Alexi Kiss, Gregory I. Goldberg, Miroslav Blumenberg, Barry L. Marmer, Tatiana Efimova, Aaron C. Koppel |
| المصدر: | American Journal of Physiology-Cell Physiology. 306:C899-C909 |
| بيانات النشر: | American Physiological Society, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Keratinocytes, Male, Pathology, medicine.medical_specialty, Skin wound, Physiology, Matrix Metalloproteinase Inhibitors, Focal adhesion, Mice, Matrix Metalloproteinase 10, Re-Epithelialization, Cell Movement, medicine, Animals, Humans, Proline rich, Cells, Cultured, Genes, Dominant, Skin, Mice, Knockout, integumentary system, Epidermis (botany), business.industry, Editorial Focus, Dipeptides, Cell Biology, Protein Kinase C-delta, Focal Adhesion Kinase 2, Gene Expression Regulation, Matrix Metalloproteinase 9, Tyrosine kinase 2, Knockout mouse, Matrix Metalloproteinase 1, Cutaneous wound, business, Wound healing, Signal Transduction |
| الوصف: | 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. |
| تدمد: | 1522-1563 0363-6143 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9044ba390a924aacc2356a8cce0b176Test https://doi.org/10.1152/ajpcell.00331.2013Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e9044ba390a924aacc2356a8cce0b176 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221563 03636143 |
|---|