title: Microvesicle-mediated transfer of microRNA-150 from monocytes to endothelial cells promotes angiogenesis.
abstract: Recent studies by our group and others show that microRNAs can be actively secreted into the extracellular environment through microvesicles (MVs) and function as secretory signaling molecules that influence the recipient cell phenotypes. Here we investigate the role of monocyte-secreted miR-150 in promoting the capillary tube formation of endothelial cells and in enhancing angiogenesis. In vitro capillary tube formation and in vivo angiogenesis assays showed that monocyte-derived MVs have strong pro-angiogenic activities. By depleting miR-150 from monocytic MVs and increasing miR-150 in MVs derived from cells that normally contain low levels of miR-150, we further demonstrated that the miR-150 content accounted for the pro-angiogenic activity of monocytic MVs in these assays. Using tumor-implanted mice and ob/ob mice as models, we revealed that miR-150 secretion, which is increased for diseases such as cancers and diabetes, significantly promotes angiogenesis. The delivery of anti-miR-150 antisense oligonucleotides into tumor-implanted mice and ob/ob mice via MVs, however, strongly reduced angiogenesis in both types of mice. Our results collectively demonstrate that secretion of miR-150 via MVs can promote angiogenesis in vitro and in vivo, and we also present a novel microRNA-based therapeutic approach for disease treatment.
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Dai
authors.forename: Wenyang
authors.initials: W
authors.lastname: Li
authors.forename: Xing
authors.initials: X
authors.lastname: Cai
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Yunxing
authors.initials: Y
authors.lastname: Xue
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Dameng
authors.initials: D
authors.lastname: Li
authors.forename: Dongxia
authors.initials: D
authors.lastname: Hou
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002450:Cell Communication; D055252:Cell-Derived Microparticles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008820:Mice, Obese; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D012334:RNA, Neoplasm; C533097:MIR150, human; C529101:Mirn150 microRNA, mouse
keywords: Angiogenesis; Atherosclerosis; Cancer; Diabetes; Endothelial Cell; MicroRNA; Microvesicle; Monocyte; miR-150