Loss of miR-29 is associated with cardiac
fibrosis. This study examined the role and therapeutic potential of miR-29 in mouse model of
hypertension induced by
angiotensin II (AngII). By using
microRNA microarray, in situ hybridization, and real-time polymerase chain reaction, we found that AngII-induced cardiac
fibrosis in the hypertensive heart and in cultured cardiac fibroblasts were associated with downregulation of miR-29a-c via a Smad3-dependent mechanism. In vitro knockdown of
miR-29b enhanced but overexpression of
miR-29b inhibited AngII-induced
fibrosis, revealing a protective role of
miR-29b in cardiac
fibrosis in response to AngII. This was further demonstrated in vivo by the ability of overexpressing
miR-29b in the mouse heart to prevent AngII-mediated cardiac
fibrosis and cardiac dysfunction. Importantly, we also found that restored
miR-29b in the established hypertensive heart was capable of blocking progressive cardiac
fibrosis and improving cardiac dysfunction, demonstrating a therapeutic potential of
miR-29b for chronic
heart disease. Further studies revealed that targeting the
transforming growth factor (TGF)-β1 coding sequence region, thereby inhibiting TGF-β/Smad3 signaling, could be a new mechanism by which
miR-29b inhibited AngII-induced cardiac
fibrosis. In conclusion,
miR-29b plays a protective role in AngII-mediated cardiac remodeling and may be a therapeutic agent for cardiac
fibrosis by targeting the TGF-β/Smad3 pathway.