Proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by MSC exosomes

Mesenchymal stem cell (MSC) exosomes have been found to attenuate cardiac systolic and diastolic dysfunction in animal models of ischemia. Exosomes carry a plethora of active and inactive proteins as their cargo, which are readily available to the recipient cell for use in intracellular signaling pathways-depending on the stresses, such as ischemia or hypoxia. Among the exosomal proteins are the often-overlooked cargo of transcriptional regulators. These transcriptional regulators influence the transcriptome and subsequently the proteome of recipient cell. Here, we report the transcriptional factors and regulators differentially modulated and their potential role in modulating cardiac function in MSC exosome treated ischemic mice hearts. Our analysis shows ischemic stress modulating transcriptional regulators and factors such as HSF1 and HIF1A in the infarct and peri-infarct areas of ischemic hearts which is mitigated by MSC exosomes. Similarly, STAT3 and SMAD3 are also modulated by MSC exosomes. Interestingly, NOTCH1 and beta-catenin were detected in the ischemic hearts. The differential expression of these regulators and factors drives changes in various biological process governed in the ischemic cardiac cells. We believe these studies will advance our understanding of cardiac dysfunction occurring in the ischemic hearts and lay the groundwork for further studies on the modulation of cardiac function during ischemia by MSC exosomes.

Automated summary

Research has shown that mesenchymal stem cell exosomes can alleviate cardiac dysfunction in animal models of ischemia. These exosomes carry active and inactive proteins, including often-overlooked transcriptional regulators, which can influence the transcriptome and proteome of recipient cells. The study investigates the differentially modulated transcriptional factors and regulators in MSC exosome-treated ischemic mouse hearts and their potential role in modulating cardiac function. The findings provide insight into the mechanisms underlying cardiac dysfunction during ischemia and pave the way for future studies on the modulation of cardiac function by MSC exosomes.