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Flow‐regulation of Vascular Smooth Muscle Cell Proliferation: Roles of Endothelial Cell‐secreted MicroRNA‐126
Author(s) -
Zhou Jing,
Li Julie Y.-S,
Chien Shu
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.870.37
Subject(s) - microbiology and biotechnology , microrna , microvesicles , gene silencing , biology , vascular smooth muscle , cell growth , angiogenesis , regulator , gene , cancer research , genetics , smooth muscle , endocrinology
MicroRNAs (miRs) are noncoding RNAs that regulate mRNA stability and translational repression. In addition to their primary intracellular locations, miRs have also been detected extracellularly in plasma and other body fluids. MiRs produced by cells can be secreted as signaling molecules to be taken up by receiving cells to result in gene silencing. We investigated the roles of miR‐126, which is an endothelial cell (EC)‐enriched key regulator for vascular integrity and angiogenesis, in regulating flow‐mediated smooth muscle cell (SMC) proliferation. The results indicate that ECs released miR‐126 into the extracellular environment to cause an increase of miR‐126 in the SMCs, and that laminar flow shear stress applied to ECs attenuated such effects. MiR‐126 is delivered as both the vesicle‐free Argonaute 2 (Ago2)/miRs complex and as the membrane‐bounded microvesicles/exosomes. After being taken up, miR‐126 in SMCs directly represses FOXO3, BCL2 and IRS1 expression and leads to the increase of SMC proliferation. Our investigation has identified potential molecular targets and their functional mechanisms responsible for the initiation and progression of vascular proliferative disorders as a result of EC/SMC interactions under static and shearing conditions. This study highlights the function of miRs as mediators for the flow shear stress‐regulated cell‐cell communications in the vascular system.