Abstract
Using transgenic cardiac Nkx2.5 enhancer-eGFP mice to label Nkx2.5+ cardiomyoblasts, an embryonic Nkx2.5+ cell population representing the common precursor for cardiovascular lineages was identified in the developing heart and a residual small population was also found in the postnatal heart. Our previous study found that A83-01, an inhibitor of TGFb receptor type I (TGFbRI), could improve cardiac function in post-injured adult heart through inducing the proliferation of Nkx2.5+ cardiomyoblasts and enhancing paracrine benefit in the enhancement of myocardial survival. The aim of the present study is to examine whether the exosome secreted from A83-01-primed Nkx2.5+ cell (exo(Nkx-A83)) could increase cardiomyocyte survival and to investigate the cardioprotective mechanism of the exosomal molecules. Adult mice cardiomyocytes were isolated and cultured in IMDM medium in vitro . A83-01 alone did not directly affect myocyte viability. The myocyte viability was 33.3±2.0 % on day 5, and could be prominently increased to be 63.8 ±0.9% when co-cultured with Nkx2.5+ cell in the presence of A83-01. The effect was abolished by GW4869 to block exosome secretion. Moreover, treating cardiomyocyte with the purified exo(Nkx-A83) could markedly increase cell viability in vitro . The miRNA microarray and qPCR validation were performed to identify the different miRNAs in the exosome secreted from Nkx2.5+ cell treated with or without A83-01. It was found the marked increase of miR-30c, miR-489, miR-92b, and miR-98 in exo(Nkx-A83). Functional study demonstrated miRNA mimics of miR-30c and miR-92b could significantly enhance myocyte survival in vitro . Furthermore, administration of the purified exo(Nkx-A83) via intravenous injection in isoprenaline-induced heart injured mice could significantly improve cardiac function monitored by echocardiography. In conclusion, the findings revealed miR-30c and miR-92b in exo(Nkx-A83) could contribute to its cardioprotective action for the enhancement of myocardial survival.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
