Literature DB >> 24838098

MFG-E8 regulates angiogenesis in cutaneous wound healing.

Akihiko Uchiyama1, Kazuya Yamada1, Sachiko Ogino1, Yoko Yokoyama1, Yuko Takeuchi1, Mark C Udey2, Osamu Ishikawa1, Sei-ichiro Motegi3.   

Abstract

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-PDGFRβ 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 PDGFRβ(+), αSMA(+), 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.
Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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Year:  2014        PMID: 24838098      PMCID: PMC4076467          DOI: 10.1016/j.ajpath.2014.03.017

Source DB:  PubMed          Journal:  Am J Pathol        ISSN: 0002-9440            Impact factor:   4.307


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