MicroRNA-221 regulates high glucose-induced endothelial dysfunction.
Persistent hyperglycemia in diabetes causes endothelial cell dysfunction. Exposure to high levels of glucose, which mimics hyperglycemia, induced expression of microRNA 221 (miR-221) but reduced expression of c-kit, the receptor for stem cell factor in human umbilical vein endothelial cells (HUVECs). In addition, high glucose treatment impaired endothelial cell migration. Incubation with the antisense miR-221 oligonucleotide AMO-221 reduced expression of miR-221 and restored c-kit protein expression in HUVECs treated with high levels of glucose. Furthermore, AMO-221 treatment abolished the inhibitory effect of high glucose exposure on HUVECs transmigration. Thus, under hyperglycemic conditions, miR-221 is induced in HUVECs, which consequently triggers inhibition of c-kit and impairment of HUVECs migration. These findings suggest that manipulation of the miR-221-c-kit pathway may offer a novel strategy for treatment of vascular dysfunction in diabetic patients.
Texas Heart Institute and The University of Texas Medical School, Heart Failure and Stem Cell, P.O. Box 20345, MC 2-255, 6770 Bertner Avenue, Houston, TX 77030, USA. Yangxin_li@yahoo.com
Yangxin
Y
Li
Yao-Hua
YH
Song
Fan
F
Li
Tong
T
Yang
Yao Wei
YW
Lu
Yong-Jian
YJ
Geng
D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis
D005947:Glucose; D035683:MicroRNAs; D019009:Proto-Oncogene Proteins c-kit; C525709:MIR221, human