1. Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.
- Author
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Adini, Irit, Ghosh, Kaustabh, Adini, Avner, Zai-Long Chi, Yoshimura, Takeru, Benny, Ofra, Connor, Kip M., Rogers, Michael S., Bazinet, Lauren, Birsner, Amy E., Bielenberg, Diane R., and D'Amato, Robert J.
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NEOVASCULARIZATION , *BLOOD-vessel development , *CYTOKINES , *EPITHELIAL cells , *HUMAN heredity , *RETINAL degeneration - 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 Ught-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 Ught-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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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