title: Myocardin-related transcription factor-A is a key regulator in retinoic acid-induced neural-like differentiation of adult bone marrow-derived mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can differentiate into neuron cells under appropriate environment in vitro and in vivo. Retinoic acid (RA), a vitamin A derivative, is known to facilitate the neuronal differentiation of MSCs. However, the mechanism by which RA induced MSC differentiation into neuron-like cells is not completely understood. Here, we show that RA can induce neural-like differentiation of bone marrow-derived MSCs, as evidenced by the increase of neuron-specific marker expression and the gradually decreased resting membrane potential. Of note, myocardin-related transcription factor-A (MRTF-A), a major co-activator of serum response factor (SRF), was significantly activated and its nuclear localization was observed during RA-induced neural-like differentiation. MRTF-A is recently reported to function in the development of the nervous system. Our results demonstrated that dominant-negative form of MRTF-A (DN-MRTF-A) or shRNA-MRTF-A strongly inhibited upregulation of neural markers in response to RA. Furthermore, reporter assays with NF-H promoter indicated that RA and MRTF-A can synergistically activate NF-H transcription and enhance the mRNA expression of NF-H. These findings reveal that MRTF-A is a key regulator in all-trans RA-induced neural-like differentiation of bone marrow-derived MSCs.
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.forename: Feng-Po
authors.initials: FP
authors.lastname: Wang
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Ma
authors.forename: Xue-Gang
authors.initials: XG
authors.lastname: Luo
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D016900:Neurofilament Proteins; D014157:Transcription Factors; C557977:myocardin-related transcription factor-A, rat; C051774:neurofilament protein H; D014212:Tretinoin