Molecular interplay between microRNA-130a and PTEN in palmitic acid-mediated impaired function of endothelial progenitor cells: Effects of metformin.
Int J Mol Med
; 43(5): 2187-2198, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30896786
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Palmítico
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MicroRNAs
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PTEN Fosfo-Hidrolase
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Células Progenitoras Endoteliais
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Metformina
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article