JOURNAL ARTICLE

miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation

Peng Che, Jun Liu, Zhen Shan, Ridong Wu, Chen Yao, Jin Cui, Xiaonan Zhu, Junwei Wang, Mary Susan Burnett, Shenming Wang, JinSong Wang
Aging Cell 2014, 13 (5): 926-34
25059272
Increasing evidence suggests that microRNAs (miRNAs) play important roles in impaired endothelial cell (EC) angiogenesis during aging. However, their exact roles in the aging process remain unclear. We aimed to determine whether miRNAs cause angiogenesis defects in ECs during aging and to uncover the underlying mechanisms. To study the miRNA-induced changes in ECs during aging, we performed microarray analyses on arterial ECs collected from young and aging mice. Using qRT-PCR, we showed that microRNA-125a-5p (mir-125a-5p) expression was approximately 2.9 times higher in old endothelial cells (OECs) compared with samples collected from young animals. Western blot assays showed a lower expression level of an mir-125a-5p target known as related transcriptional enhancer factor-1 (RTEF-1) in OECs compared with its expression levels in young cells. Overexpression of mir-125a-5p in young endothelial cells (YECs) using pre-mir-125a-5p caused the downregulation of RTEF-1, endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) and resulted in impaired angiogenesis, as evidenced by spheroid sprouting and tube formation assays in vitro. Conversely, repression of mir-125a-5p in OECs using anti-mir-125a-5p increased RTEF-1, eNOS and VEGF expression and improved EC angiogenesis. Importantly, impaired angiogenesis caused by knock-down of RTEF-1 was not efficiently rescued by anti-mir-125a-5p. Dual-luciferase reporter gene analysis showed that RTEF-1 is a direct target of mir-125a-5p, which regulates angiogenesis by repressing RTEF-1 expression and modulating eNOS and VEGF expression. These findings indicate that mir-125a-5p and RTEF-1 are potential therapeutic targets for improving EC-mediated angiogenesis in elderly individuals.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
25059272
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"