Downregulation of MicroRNA-130a Contributes to Endothelial Progenitor Cell Dysfunction in Diabetic Patients via Its Target Runx3
نویسندگان
چکیده
Dysfunction of endothelial progenitor cells (EPCs) contributes to diabetic vascular disease. MicroRNAs (miRs) have emerged as key regulators of diverse cellular processes including angiogenesis. We recently reported that miR-126, miR-130a, miR-21, miR-27a, and miR-27b were downregulated in EPCs from type II diabetes mellitus (DM) patients, and downregulation of miR-126 impairs EPC function. The present study further explored whether dysregulated miR-130a were also related to EPC dysfunction. EPCs were cultured from peripheral blood mononuclear cells of diabetic patients and healthy controls. Assays on EPC function (proliferation, migration, differentiation, apoptosis, and colony and tubule formation) were performed. Bioinformatics analyses were used to identify the potential targets of miR-130a in EPCs. Gene expression of miR-103a and Runx3 was measured by real-time PCR, and protein expression of Runx3, extracellular signal-regulated kinase (ERK), vascular endothelial growth factor (VEGF) and Akt was measured by Western blotting. Runx3 promoter activity was measured by luciferase reporter assay. A miR-130a inhibitor or mimic and lentiviral vectors expressing miR-130a, or Runx3, or a short hairpin RNA targeting Runx3 were transfected into EPCs to manipulate miR-130a and Runx3 levels. MiR-130a was decreased in EPCs from DM patients. Anti-miR-130a inhibited whereas miR-130a overexpression promoted EPC function. miR-130a negatively regulated Runx3 (mRNA, protein and promoter activity) in EPCs. Knockdown of Runx3 expression enhanced EPC function. MiR-130a also upregulated protein expression of ERK/VEGF and Akt in EPCs. In conclusion, miR-130a plays an important role in maintaining normal EPC function, and decreased miR-130a in EPCs from DM contributes to impaired EPC function, likely via its target Runx3 and through ERK/VEGF and Akt pathways.
منابع مشابه
Simultaneous Effect of Resistance Training and Endothelial Progenitor Cell Injection on the Expression of Vegf Angiogenic Factor and Its Relationship with Insulin Resistance in Diabetic Male Rats Induced By Stz
Background: Exercise and the simultaneous use of progenitor cells is a new strategy aimed for reducing diabetic disorders. One of the known mechanisms is angiogenic disorders caused by diabetes. Therefore, the present study was performed to determine the simultaneous effect of resistance training with endothelial progenitor cell injection on the expression of angiogenic factors in the skeletal ...
متن کاملThe Effect of Combining Resistance Training and Endothelial Progenitor Cell Injection on the Expression of Angiogenic Factors In Diabetic Male Rats Induced By Stz
Background: Angiogenesis disorders are known mechanisms of diabetes. With the aim of reducing angiogenesis disorders, resistance training and its combination with endothelial progenitor cell injection are new strategies. Therefore, the present study was performed to determine the effect of resistance training with endothelial progenitor cell injection on the expression of angiogenic factors in ...
متن کاملEndothelial Progenitor Cell Dysfunction in Polycystic Ovary Syndrome: Implications for The Genesis of Cardiovascular Diseases
متن کامل
Chronic Exposure of Human Endothelial Progenitor Cells to Diabetic Condition Abolished the Regulated Kinetics Activity of Exosomes
By virtue of lifestyle change, incidence of type 2 diabetes is increasingly being raised with different up-surging pathologies. This condition found to disqualify endothelial progenitor cells during neo-vascularization. Besides to an aborted differentiation property, malfunctioned paracrine activities exacerbate vascular abnormalities. It is found nano-scaled exosomes play essential roles on re...
متن کاملChronic Exposure of Human Endothelial Progenitor Cells to Diabetic Condition Abolished the Regulated Kinetics Activity of Exosomes
By virtue of lifestyle change, incidence of type 2 diabetes is increasingly being raised with different up-surging pathologies. This condition found to disqualify endothelial progenitor cells during neo-vascularization. Besides to an aborted differentiation property, malfunctioned paracrine activities exacerbate vascular abnormalities. It is found nano-scaled exosomes play essential roles on re...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 8 شماره
صفحات -
تاریخ انتشار 2013