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Endothelial Cell‐Dependent miR‐145 Expression Regulates TGFβ Signaling in Vascular Smooth Muscle Cells
Author(s) -
Lilly Brenda,
Zhao Ning
Publication year - 2013
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.27.1_supplement.526.5
Subject(s) - microbiology and biotechnology , vascular smooth muscle , microrna , signal transduction , transforming growth factor , endothelial stem cell , myocyte , cell , chemistry , cell type , smooth muscle , biology , endocrinology , gene , biochemistry , in vitro
Blood vessel formation is a tightly regulated process that serves a critical role in both health and disease. Our lab has focused on the interactions between endothelial and smooth muscle cells that regulate proper blood vessel formation and function. In doing so, we identified miR‐145 as a microRNA that is robustly induced in vascular smooth muscle cells by endothelial cells. miR‐145 has been implicated in having an important role in the differentiation of smooth muscle cells. Our data show that miR‐145 is regulated by Notch signaling in smooth muscle cells, and when overexpressed leads to reduced migration. To investigate the underlying mechanisms, we searched for predicted targets of miR‐145 and identified TGFβ receptor II (TGFBR2) as a possible target. Overexpression of miR‐145 mimic and luciferase assays using the 3′‐UTR of TGFBR2 confirmed it is a direct target of miR‐145. Our results indicate that endothelial cell‐induced miR‐145 is regulated by Notch signaling, and once induced has the capacity to regulate TGFß signaling in smooth muscle cells. These data suggest that within smooth muscle cells miR‐145 acts to selectively regulate the TGFß pathway to govern smooth muscle function. Funded by AHA and Nationwide Children's Hospital.