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MicroRNA‐195a‐3p inhibits angiogenesis by targeting Mmp2 in murine mesenchymal stem cells
Author(s) -
Gao Fan,
Sun Meng,
Gong Yumei,
Wang Haiyan,
Wang Yusheng,
Hou Huiyuan
Publication year - 2016
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.22638
Subject(s) - angiogenesis , biology , mesenchymal stem cell , mmp2 , microrna , neovascularization , gene silencing , cancer research , microbiology and biotechnology , matrix metalloproteinase , stem cell , immunology , downregulation and upregulation , genetics , gene
SUMMARY 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 .