| First Author | Uchiyama A | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 7 | Pages | 1981-90 |
| PubMed ID | 24838098 | Mgi Jnum | J:213510 |
| Mgi Id | MGI:5585217 | Doi | 10.1016/j.ajpath.2014.03.017 |
| Citation | Uchiyama A, et al. (2014) MFG-E8 regulates angiogenesis in cutaneous wound healing. Am J Pathol 184(7):1981-90 |
| abstractText | Our research group recently demonstrated that pericytes are major sources of the secreted glycoprotein and integrin ligand lactadherin (MFG-E8) in B16 melanoma tumors, and that MFG-E8 promotes angiogenesis via enhanced PDGF-PDGFRbeta signaling mediated by integrin-growth factor receptor crosstalk. However, sources of MFG-E8 and its possible roles in skin physiology are not well characterized. The objective of this study was to characterize the involvement of MFG-E8 in skin wound healing. In the dermis of normal murine and human skin, accumulations of MFG-E8 were found around CD31(+) blood vessels, and MFG-E8 colocalized with PDGFRbeta(+), alphaSMA(+), and NG2(+) pericytes. MFG-E8 protein and mRNA levels were elevated in the dermis during full-thickness wound healing in mice. MFG-E8 was diffusely present in granulation tissue and was localized around blood vessels. Wound healing was delayed in MFG-E8 knockout mice, compared with the wild type, and myofibroblast and vessel numbers in wound areas were significantly reduced in knockout mice. Inhibition of MFG-E8 production with siRNA attenuated the formation of capillary-like structures in vitro. Expression of MFG-E8 in fibrous human granulation tissue with scant blood vessels was less than that in granulation tissue with many blood vessels. These findings suggest that MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis. |
