miR-10a contributes to retinoid acid-induced smooth muscle cell differentiation.
MicroRNAs (miRs) have been reported to play a critical role in muscle differentiation and function. The purpose of this study is to determine the role of miRs during smooth muscle cell (SMC) differentiation from embryonic stem cells (ESCs). MicroRNA profiling showed that miR-10a expression is steadily increased during in vitro differentiation of mouse ESCs into SMCs. Loss-of-function approaches using miR-10a inhibitors uncovered that miR-10a is a critical mediator for SMC lineage determination in our retinoic acid-induced ESC/SMC differentiation system. In addition, we have documented for the first time that histone deacetylase 4 is a novel target of miR-10a and mediates miR-10a function during ESC/SMC differentiation. To determine the molecular mechanism through which retinoic acid induced miR-10a expression, a consensus NF-kappaB element was identified in the miR-10a gene promoter by bioinformatics analysis, and chromatin immunoprecipitation assay confirmed that NF-kappaB could bind to this element. Finally, inhibition of NF-kappaB nuclear translocation repressed miR-10a expression and decreased SMC differentiation from ESCs. Our data demonstrate for the first time that miR-10a is a novel regulator in SMC differentiation from ESCs. These studies suggest that miR-10a may play important roles in vascular biology and have implications for the diagnosis and treatment of vascular diseases.
Huang
Huarong
H
Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109.
Xie
Changqing
C
Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109.
Sun
Xuan
X
Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109; Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha 410078, China.
Ritchie
Raquel P
RP
Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109.
Zhang
Jifeng
J
Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109.
Chen
Y Eugene
YE
Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109. Electronic address: echenum@umich.edu.
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods; D053595:Embryonic Stem Cells / Q000166:cytology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009130:Muscle, Smooth / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000378:metabolism*; D014652:Vascular Diseases / Q000378:metabolism
D035683:MicroRNAs; D016328:NF-kappa B; D014212:Tretinoin