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


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).


CONCLUSIONS
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.
Department of Pharmacology and School of Pharmacy, Second Military Medical University, Shanghai, China. ruiyaocheng@yahoo.com
Dong
D
Li
Pengyuan
P
Yang
Qinghui
Q
Xiong
Xuhui
X
Song
Xiangqun
X
Yang
Lin
L
Liu
Wenjun
W
Yuan
Yao-Cheng
YC
Rui
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014666:Vasomotor System / Q000502:physiology
D014408:Biomarkers, Tumor; D019332:Endothelin-1; D008077:Lipoproteins, LDL; C509207:MIRN124 microRNA, human; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C099252:oxidized low density lipoprotein