title: Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.
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.
authors.forename: Irit
authors.initials: I
authors.lastname: Adini
authors.forename: Kaustabh
authors.initials: K
authors.lastname: Ghosh
authors.forename: Avner
authors.initials: A
authors.lastname: Adini
authors.forename: Zai-Long
authors.initials: ZL
authors.lastname: Chi
authors.forename: Takeru
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Ofra
authors.initials: O
authors.lastname: Benny
authors.forename: Kip M
authors.initials: KM
authors.lastname: Connor
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rogers
authors.forename: Lauren
authors.initials: L
authors.lastname: Bazinet
authors.forename: Amy E
authors.initials: AE
authors.lastname: Birsner
authors.forename: Diane R
authors.initials: DR
authors.lastname: Bielenberg
authors.forename: Robert J
authors.initials: RJ
authors.lastname: D'Amato
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D000071235:Fibromodulin; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000378:metabolism*; D012880:Skin Pigmentation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604332:Fmod protein, mouse; D011509:Proteoglycans; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D000071235:Fibromodulin