MicroRNA-145 Regulates Pathological Retinal Angiogenesis by Suppression of TMOD3.

Authors:
Chi-Hsiu Liu
Chi-Hsiu Liu
National Taiwan University
Taiwan
Zhongxiao Wang
Zhongxiao Wang
Shanghai Institute of Technology
China
Shuo Huang
Shuo Huang
Arizona State University
United States
Ye Sun
Ye Sun
University of Wisconsin-Madison
United States
Jing Chen
Jing Chen
University of Kentucky
Lexington | United States

Mol Ther Nucleic Acids 2019 Mar 21;16:335-347. Epub 2019 Mar 21.

Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. Electronic address:

Pathological angiogenesis is a hallmark of various vascular diseases, including vascular eye disorders. Dysregulation of microRNAs (miRNAs), a group of small regulatory RNAs, has been implicated in the regulation of ocular neovascularization. This study investigated the specific role of microRNA-145 (miR-145) in regulating vascular endothelial cell (EC) function and pathological ocular angiogenesis in a mouse model of oxygen-induced retinopathy (OIR). Expression of miR-145 was significantly upregulated in OIR mouse retinas compared with room air controls. Treatment with synthetic miR-145 inhibitors drastically decreased levels of pathological neovascularization in OIR, without substantially affecting normal developmental angiogenesis. In cultured human retinal ECs, treatment with miR-145 mimics significantly increased the EC angiogenic function, including proliferation, migration, and tubular formation, whereas miR-145 inhibitors attenuated in vitro angiogenesis. Tropomodulin3 (TMOD3), an actin-capping protein, is a direct miR-145 target and is downregulated in OIR retinas. Treatment with miR-145 mimic led to TMOD3 inhibition, altered actin cytoskeletal architecture, and elongation of ECs. Moreover, inhibition of TMOD3 promoted EC angiogenic function and pathological neovascularization in OIR and abolished the vascular effects of miR-145 inhibitors in vitro and in vivo. Overall, our findings indicate that miR-145 is a novel regulator of TMOD3-dependent cytoskeletal architecture and pathological angiogenesis and a potential target for development of treatments for neovascular eye disorders.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S21622531193005
Publisher Site
http://dx.doi.org/10.1016/j.omtn.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460252PMC
March 2019
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