Wound healing in the alpha2beta1 integrin-deficient mouse: altered keratinocyte biology and dysregulated matrix metalloproteinase expression.
The alpha2beta1 integrin, a collagen/laminin receptor, is expressed at high level in the basal cell layer of the epidermis. To define the role of the alpha2beta1 integrin in wound healing, wound repair was extensively evaluated in wild-type and alpha2-null mice in vivo. In addition, the impact of alpha2beta1 integrin-deficiency on the function of primary murine keratinocytes in vitro was analyzed. Our in vivo findings demonstrate that genetic deletion of the alpha2beta1 integrin does not significantly alter the rate of re-epithelialization, collagen deposition, or tensile strength during wound closure in mice. In marked contrast to the observed similarities in wound healing, deletion of the alpha2beta1 integrin resulted in a dramatic increase in neoangiogenesis in the wound microenvironment. In contrast to in vivo studies, primary keratinocytes from alpha2-null mice adhered poorly and displayed impaired migration on type I collagen in vitro. We demonstrate that alpha2beta1 integrin-ligation negatively regulates expression of genes including matrix metalloproteinases both in vivo and in vitro. Furthermore, the changes in gene expression could potentially account for relatively normal wound healing in the alpha2-deficient mouse and our recent observation that suggests an antiangiogenic role for the alpha2beta1 integrin in vivo.
Grenache
David G
DG
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, USA.
Zhang
Zhonghua
Z
Wells
Laura E
LE
Santoro
Samuel A
SA
Davidson
Jeffrey M
JM
Zutter
Mary M
MM
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D015870:Gene Expression; D038982:Integrin alpha2beta1 / Q000172:deficiency*; D015603:Keratinocytes; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D012867:Skin / Q000293:injuries*; D014945:Wound Healing / Q000235:genetics; D014950:Wounds, Penetrating / Q000503:physiopathology*
D038982:Integrin alpha2beta1; D020782:Matrix Metalloproteinases