| First Author | Deng M | Year | 2006 |
| Journal | Mol Biol Cell | Volume | 17 |
| Issue | 8 | Pages | 3446-55 |
| PubMed ID | 16760432 | Mgi Jnum | J:113435 |
| Mgi Id | MGI:3686579 | Doi | 10.1091/mbc.E06-02-0102 |
| Citation | Deng M, et al. (2006) A role for the mitogen-activated protein kinase kinase kinase 1 in epithelial wound healing. Mol Biol Cell 17(8):3446-55 |
| abstractText | The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell-cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and metalloproteinase III. Our data suggest that MEKK1 transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization. |
