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- Title
miR-92a Corrects CD34+ Cell Dysfunction in Diabetes by Modulating Core Circadian Genes Involved in Progenitor Differentiation.
- Authors
Bhatwadekar, Ashay D.; Yuanqing Yan; Stepps, Valerie; Hazra, Sugata; Korah, Maria; Bartelmez, Stephen; Chaqour, Brahim; Grant, Maria B.; Yan, Yuanqing
- Abstract
Autologous CD34(+) cells are widely used for vascular repair; however, in individuals with diabetes and microvascular disease these cells are dysfunctional. In this study, we examine expression of the clock genes Clock, Bmal, Per1, Per2, Cry1, and Cry2 in CD34(+) cells of diabetic and nondiabetic origin and determine the small encoding RNA (miRNA) profile of these cells. The degree of diabetic retinopathy (DR) was assessed. As CD34(+) cells acquired mature endothelial markers, they exhibit robust oscillations of clock genes. siRNA treatment of CD34(+) cells revealed Per2 as the only clock gene necessary to maintain the undifferentiated state of CD34(+) cells. Twenty-five miRNAs targeting clock genes were identified. Three of the miRNAs (miR-18b, miR-16, and miR-34c) were found only in diabetic progenitors. The expression of the Per2-regulatory miRNA, miR-92a, was markedly reduced in CD34(+) cells from individuals with DR compared with control subjects and patients with diabetes with no DR. Restoration of miR-92a levels in CD34(+) cells from patients with diabetes with DR reduced the inflammatory phenotype of these cells and the diabetes-induced propensity toward myeloid differentiation. Our studies suggest that restoring levels of miR-92a could enhance the usefulness of CD34(+) cells in autologous cell therapy.
- Subjects
CD34 antigen; GENETICS of circadian rhythms; PROGENITOR cells; CELL differentiation; DIABETIC retinopathy; CLOCK genes; RNA; INFLAMMATION; PROTEIN metabolism; RNA metabolism; ANTIGENS; BIOCHEMISTRY; CELL culture; CELL receptors; DIABETES; ENDOTHELIUM; GENES; GLYCOPROTEINS; LONGITUDINAL method; PHENOMENOLOGY; PEPTIDES; PROTEINS; RESEARCH funding; GENE expression profiling; CHEMICAL inhibitors
- Publication
Diabetes, 2015, Vol 64, Issue 12, p4226
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-0521