MicroRNA-125a/b-5p inhibits endothelin-1 expression in... : Journal of Hypertension (original) (raw)

Original papers: Endothelium

MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells

Li, Donga,b,*; Yang, Pengyuana,c,*; Xiong, Qinghuia; Song, Xuhuia; Yang, Xiangqund; Liu, Lind; Yuan, Wenjunb,e; Rui, Yao-Chenga

aDepartment of Pharmacology and School of Pharmacy, China

bDepartment of Physiology, China

cNational Key Laboratory of Medical Immunology and Institute of Immunology, China

dDepartment of Anatomy, Second Military Medical University, Shanghai, China

eDepartment of Physiology and Neurobiology, Ningxia Medical University, Yinchuan, China

*D.L. and P.Y. contributed equally to the writing of the article.

Received 7 October, 2009

Revised 1 March, 2010

Accepted 24 March, 2010

Correspondence to Yao-Cheng Rui, Department of Pharmacology and School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China Tel/fax: +86 21 81871273; e-mail: [email protected]

Co-correspondence to Wenjun Yuan E-mail: [email protected]

Abstract

Background

Endothelin-1 (ET-1) is considered to be one of the most potent and long-lasting vasoconstrictive peptides, but the mechanisms on the regulation of ET-1 expression are not fully understood.

Method and results

In this study, we found that microRNA (miR)-125a-5p and miR-125b-5p are highly expressed in vascular endothelial cells (VECs), which can be regulated by oxidized low-density lipoprotein (oxLDL). To explore the function of miR-125a/b-5p in VECs, we examined the roles of potential targets of miR-125a/b-5p that could influence endothelium function. We found that both miR-125a/b-5p can suppress oxLDL-induced ET-1 expression by directly targeting 3′ untranslated region of prepro-endothelin-1 (preproET-1) mRNA determined by luciferase reporter assay, western blot, and enzyme immunometric assay. Consistently, inhibitors of miR-125a/b-5p can directly enhance preproET-1 expression. The decreased expressions of miR-125a-5p and miR-125b-5p are negatively associated with upregulation of preproET-1 expression in aorta of stroke-prone spontaneously hypertensive rats (SHR-SPs).

Conclusion

Our finding demonstrated that endothelial miR-125a/b-5p inhibits ET-1 expression in VECs, which revealed a novel miRNA-mediated mechanism in vasomotor homeostasis.