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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

Authors: 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

Published In Mol Biol Cell, (2006 Aug)

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.

PubMed ID: 16760432 Exiting the NIEHS site

MeSH Terms: Activins/metabolism; Animals; Animals, Newborn; Cell Movement; Cornea/cytology; Enzyme Activation; Epidermal Cells; Epidermis/pathology; Epithelial Cells/cytology; Epithelium/enzymology*; Epithelium/physiology*; Extracellular Matrix/metabolism; Gene Expression; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; Keratinocytes/cytology; MAP Kinase Kinase Kinase 1/metabolism*; Mice; Mice, Inbred C57BL; Skin/cytology; Skin/pathology; Wound Healing/immunology*

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Last Reviewed: October 02, 2024