Molecular interplay between microRNA-130a and PTEN in palmitic acid-mediated impaired function of endothelial progenitor cells: Effects of metformin.

ABSTRACT

Metformin serves an important role in improving the functions of endothelial progenitor cells (EPCs). MicroRNAs (miRNAs), small non­coding RNAs, have been investigated as significant regulators of EPC vascular functions. The present study investigated the molecular crosstalk between metformin and miRNA­130a (miR­130a) in the functions of EPCs exposed to palmitic acid (PA). Isolated EPCs were treated with metformin, PA, and metformin + PA, respectively. Cell Counting Kit­8, Transwell and Matrigel assays were performed to detect the proliferation, migration and tube formation ability of EPCs following different treatments. The expression of miR­130a, phosphatase and tensin homolog (PTEN) and phosphorylated­AKT was analyzed by reverse transcription­quantitative polymerase chain reaction and western blotting. The specific mechanism underlying the function of metformin in EPCs was further elucidated by transfecting miR­130a mimics and inhibitor to overexpress and inhibit the expression of miR­130a in EPCs, respectively. EPCs exhibited impaired functions of proliferation (P<0.01 compared with the control), migration (P<0.01 compared with the control) and tube formation (P<0.01 compared with the control) following treatment with PA, and the expression levels of miR­130a and PTEN were decreased and increased, respectively. However, the presence of metformin, or the overexpression of miR­130a using miR­130a mimic alleviated the impairment of angiogenesis and proliferation, decreased the expression of PTEN and activated the phosphoinositide­3 kinase/AKT pathway in EPCs exposed to PA. By contrast, downregulating the expression of miR­130a with a miR­130a inhibitor reversed the metformin­mediated protection. These results demonstrate the beneficial effect of miR­130a/PTEN on EPC functions, which can be regulated by metformin. The effects of metformin on improving PA­induced EPC dysfunction are mediated by miR­130a and PTEN, which may assist in the prevention and/or treatment of diabetic vascular disease.