title: MicroRNA-195a-3p inhibits angiogenesis by targeting Mmp2 in murine mesenchymal stem cells.
abstract: MicroRNAs (miRNAs) modulate complex physiological and pathological processes, including the regulation of angiogenesis. Our previous study reported that bone marrow-derived mesenchymal stem cells (MSCs) are recruited into choroidal neovascularization lesions. miRNA-195 is highly expressed in MSCs, but its function remains unknown. In the present study, miR-195a-3p abundance was significantly decreased in hypoxia-treated murine MSCs; on the other hand, its overexpression reduced MSC proliferation and migration while increasing the activation of anti-angiogenic factor pigment epithelium-derived factor (PEDF). We further discovered that matrix metalloproteinase 2 (Mmp2) transcript is a target of miR-195a-3p, and that silencing Mmp2 phenocopied the reduced proliferation and migration of MSCs. The therapeutic potential of miR-195a-3p as an angiogenesis inhibitor was also demonstrated in a laser-induced choroidal neovascularization mouse model. These findings collectively indicate that miR-195a-3p is a negative modulator of angiogenesis, and could be used as an angiogenesis inhibitor. Mol. Reprod. Dev. 83: 413-423, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Cardiology, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Cardiovascular Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Hou
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D020778:Matrix Metalloproteinase 2; D035683:MicroRNAs; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C569389:MIRN195a microRNA, mouse; C522362:Mmp2 protein, mouse