Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment

J Clin Invest. 2014 Jan;124(1):425-36. doi: 10.1172/JCI69404. Epub 2013 Dec 20.

Abstract

Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in African-Americans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays. Additionally, FMOD enhanced vascular sprouting during normal retinal development. Deletion of Fmod in albino mice resulted in a marked reduction in the amount of neovascularization induced by retinal vein occlusion, corneal growth factor pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for epidemiological differences between light-skinned individuals of mixed European descent and African-Americans. Furthermore, inhibition of FMOD in humans has potential as a therapeutic strategy for treating angiogenesis-dependent diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Extracellular Matrix Proteins / metabolism*
  • Fibromodulin
  • Humans
  • Melanocytes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic*
  • Proteoglycans / metabolism*
  • Skin Pigmentation
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Extracellular Matrix Proteins
  • FMOD protein, human
  • Fmod protein, mouse
  • Proteoglycans
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Fibromodulin