A role for the mitogen-activated protein kinase kinase kinase 1 in epithelial wound healing

作者：Deng, Maoxian; Chen, Wei-Li; Takatori, Atsushi; Peng, Zhimin; Zhang, Lin; Mongan, Maureen; Parthasarathy, Ranjani; Sartor, Maureen; Miller, Marian; Yang, Jianhua; Su, Bing; Kao, Winston W. -Y.; Xia, Ying^*

来源：Molecular Biology of the Cell, 2006, 17(8): 3446-3455.

DOI：10.1091/mbc.E06-02-0102

• EXTRACELLULAR-MATRIX PROTEINS
• JNK SIGNALING PATHWAY
• GROWTH-FACTOR-BETA
• MEK KINASE 1
• CELL-MIGRATION
• EXPRESSION
• ACTIVIN
• MICE
• THROMBOSPONDIN-1
• KERATINOCYTES

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.

• 出版日期2006-8
• 单位南方医科大学