[HTML][HTML] Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment
The Journal of clinical investigation, 2014•Am Soc Clin Investig
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 …
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 …
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.
The Journal of Clinical Investigation