MFG-E8 regulates angiogenesis in cutaneous wound healing

Am J Pathol. 2014 Jul;184(7):1981-90. doi: 10.1016/j.ajpath.2014.03.017. Epub 2014 May 15.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / physiology*
  • Cell Line
  • Dermis / physiology*
  • Granulation Tissue / physiology
  • Human Umbilical Vein Endothelial Cells / cytology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Milk Proteins
  • Myocytes, Smooth Muscle / cytology
  • Myofibroblasts / cytology
  • Neovascularization, Physiologic*
  • Pericytes / cytology
  • Skin Physiological Phenomena*
  • Wound Healing*


  • Antigens, Surface
  • MFGE8 protein, human
  • Milk Proteins