RXRα and MRTF‐A have a synergistic effect in the retinoic acid‐induced neural‐like differentiation of adult bone marrow‐derived mesenchymal stem cells

Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can transform into neuron cells under an appropriate environment. Retinoic acid (RA) facilitates the neuronal differentiation of MSCs. We found that RXRalpha, a RA receptor, was significantly upregulated in RA-induced process. Here, we show that RXRalpha collaborated with myocardin-related transcription factor-A (MRTF-A) to strongly promote the RA-induced process as evidenced by the increase in NF-H expression and NF-H promoter transcription activity. Our studies reveal that RXRalpha and MRTF-A exhibit protein interactions and synergistically inhibit the MSCs apoptosis by enhancing the P21 expression. Furthermore, RXRalpha and MRTF-A can activate P21 transcription by affecting the formation of the MRTF-A/RXRalpha/RARE complex. These findings reveal the important roles of RXRalpha and MRTF-A signaling in RA-induced neural-like differentiation of MSCs and describe a new mechanism underlying the synergistic interaction of RXRalpha and MRTF-A.