Induction of meglumine adenosine cyclophosphate on bone marrow mesenchymal stem cells differentiating into cardiomyocytes and the mechanism

LI Dan; ZHANG Jin-guo; WEI Xi-qing; LIU Yan-song

doi:10.3969/j.issn.1002-266X.2015.42.001

Abstract：Objective To investigate the mechanism of meglumine adenosine cyclophosphate ( MCA) inducing the bone marrow mesenchymal stem cells ( BMSCs ) differentiating into cardiomyocytes .Methods BMSCs were cultured in vitro, and the third generation of BMSCs were inoculated into 96 hole boards , which were then divided into the control group, MCA group and MCA +LY294002 group.The MCA group was added with 1 ×10 -3 mmol/L MCA , the MCA +LY294002 group was added with PI3K/AKT signaling pathway specific inhibitor 30 min pretreated with LY294002, and then was added with 1 ×10 -3 mmol/L MCA.After induction for 3 days, the conventional culture medium was used in the two groups to continue the culture .The control group was not treated .After 4 weeks, the mRNA expression of myocardial specific GATA gene binding protein 4 (GATA-4) and gap junction protein 43 (Cx43) was detected by fluorescence quanti-tative PCR.The expression of PI3K/AKT pathway related proteins in each group , including phosphatidylinositol 3-kinase (PI3K), serine/threonine protein kinase (Akt), a forked head transcription factor O subtype (p-Foxo3a) and the DOK family proteins (DOK5), was detected by Western blotting.Results The expression of GATA-4 and CX43 mRNA in the MCA group and MCA +LY294002 group was higher than that of the control group (all P<0.01), the expression of GA-TA-4 and CX43 mRNA in the MCA +LY294002 group was lower than that in the MCA group ( all P<0 .01 ) .The ex-pression of PI3K, p-AKT, p-Foxo3a and DOK5 in the MCA group was higher than that in the control group and MCA +LY294002 group (all P<0.01).Conclusion MCA can induce BMSCs differentiating into cardiomyocytes , and its mech-anism may be related to the activation of PI3K/AKT signaling pathway.