title: A secreted MMP is required for reepithelialization during wound healing.
abstract: Matrix metalloproteinases (MMPs) are extracellular proteases highly expressed at wound sites. However, the precise function of MMPs during reepithelialization in vivo has been elusive in mammalian models because of the high level of redundancy among the 24 mammalian MMPs. For this reason we used Drosophila melanogaster, whose genome encodes only two MMPs-one secreted type (Mmp1) and one membrane-anchored type (Mmp2)-to study the function and regulation of the secreted class of MMPs in vivo. In the absence of redundancy, we found that the Drosophila secreted MMP, Mmp1, is required in the epidermis to facilitate reepithelialization by remodeling the basement membrane, promoting cell elongation and actin cytoskeletal reorganization, and activating extracellular signal-regulated kinase signaling. In addition, we report that the jun N-terminal kinase (JNK) pathway upregulates Mmp1 expression after wounding, but that Mmp1 is expressed independent of the JNK pathway in unwounded epidermis. When the JNK pathway is ectopically activated to overexpress Mmp1, the rate of healing is accelerated in an Mmp1-dependent manner. A primary function of Mmp1, under the control of the JNK pathway, is to promote basement membrane repair, which in turn may permit cell migration and the restoration of a continuous tissue.
authors.affiliation: Department of Cell and Developmental Biology and Program in Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Stevens
authors.forename: Andrea
authors.initials: A
authors.lastname: Page-McCaw
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; D020781:Matrix Metalloproteinase 1