Poster abstracts

Poster number 89 submitted by Ning Zhao

Endothelial cell-dependent Mir-145 expression regulates TGFβ signaling in vascular smooth muscle cells

Ning Zhao (Center for cardiovascular and pulmonary research, Nationwide Childrens Hospital), Brenda Lilly (Center for cardiovascular and pulmonary research, Nationwide Childrens Hospital)

Abstract:
Endothelial cell-dependent Mir-145 expression regulates TGFβ signaling in vascular smooth muscle cells

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 TGFβ signaling and matrix synthesis. TGFβ signaling is known to promote differentiation and matrix synthesis of vascular smooth muscle. The reduced TGFβ signaling by miR-145 only inhibits matrix synthesis, not differentiation. To investigate the underlying mechanisms, we searched for predicted targets of miR-145 and found TGFβ receptor II as a putative target. Overexpression of miR-145 mimic and luciferase assays using the 3’-UTR of the gene confirmed it is a direct target of miR-145. Our results indicate that endothelial cell-induced miR-145 is regulated by Notch signaling in smooth muscle cells, and once induced has the capacity to selectively regulate TGFβ signaling-dependent matrix synthesis.

Keywords: smooth muscle cell, miR-145, TGF