MiR-124 Promote Neurogenic Transdifferentiation of Adipose Derived Mesenchymal Stromal Cells Partly through RhoA/ROCK1, but Not ROCK2 Signaling Pathway

• Published in: PloS one 2016-01, Vol.11 (1), p.e0146646-e0146646
• Main Authors: Wang, Ye, Wang, Desheng, Guo, Dawen
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Animals; Bone marrow; Cell culture; Cell differentiation; Cell Transdifferentiation; Cells, Cultured; Cellular signal transduction; Fibroblasts; Gene expression; Genetic aspects; Glial fibrillary acidic protein; Health aspects; HEK293 Cells; Humans; Kinases; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; MicroRNA; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Morphology; mRNA; Neurogenesis; Neurological diseases; Neuronal-glial interactions; Neurons; Neurons - cytology; Neurons - metabolism; Neurosciences; Patch-Clamp Techniques; Phosphopyruvate hydratase; Plasmids; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Regenerative medicine; Rho-associated kinase; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - genetics; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - antagonists & inhibitors; rhoA GTP-Binding Protein - genetics; rhoA GTP-Binding Protein - metabolism; RhoA protein; RNA Interference; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Rodents; Signal Transduction; Signaling; Stem cells; Stromal cells; Studies; Tubulin; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146646

Some recent studies suggest that multiple miRNAs might regulate neurogenic transdifferentiation of mesenchymal stromal cells (MSCs). In the present study, we hypothesized that the miR-124 can repress the expression of RhoA upon the neurogenesis of adipose derived MSCs (ADMSCs). MiRNA expression dynamics during neurogenic transdifferentiation of ADMSCs were measured. The expression of neuron-specific enolase (NSE), Tuj-1 (Neuron-specific class III beta-tubulin) and glial fibrillary acidic protein (GFAP), as well as electrophysiological properties, were detected after neurogenic transdifferentiation. The targeting of miR-124 over RhoA was verified by dual luciferase assay, qRT-PCR and western blot. The functions of miR-124 and the RhoA/ROCK signaling pathway were studied using gain and loss of function experiments in vitro. MiR-124 is significantly upregulated during neurogenic transdifferentiation of ADMSCs. Knockdown of endogenous miR-124 hampered neurogenic transdifferentiation and the acquired electrophysiological properties. MiR-124 could directly target RHOA mRNA and repress its expression, through which it increased the proportion of transdifferentiated (transdiff.) cells with positive NSE, Tuj-1 and GFAP. RhoA/ROCK1, but not ROCK2 is a downstream signaling pathway of miR-124 in the process of transdifferentiation. MiR-124 is an important miRNA modulating neurogenic transdifferentiation of ADMSCs at least partly via the miR-124/RhoA/ROCK1 signaling pathway. These findings provided some fundamental information for future use of ADMSCs as an agent for regenerative medicine and cell therapy for neurological diseases.