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


ABSTRACT: 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.

SUBMITTER: Deng M 

PROVIDER: S-EPMC1525243 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

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

Deng Maoxian M   Chen Wei-Li WL   Takatori Atsushi A   Peng Zhimin Z   Zhang Lin L   Mongan Maureen M   Parthasarathy Ranjani R   Sartor Maureen M   Miller Marian M   Yang Jianhua J   Su Bing B   Kao Winston W-Y WW   Xia Ying Y  

Molecular biology of the cell 20060607 8


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  ...[more]

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