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 pa...

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Main Authors: Rajshekhar A. Kore, Samir V. Jenkins, Azemat Jamshidi-Parsian, Alan J. Tackett, Robert J. Griffin, Srinivas Ayyadevara, Jawahar L. Mehta
Format: Article
Language:English
Published: Elsevier 2023-07-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580823000444
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author Rajshekhar A. Kore
Samir V. Jenkins
Azemat Jamshidi-Parsian
Alan J. Tackett
Robert J. Griffin
Srinivas Ayyadevara
Jawahar L. Mehta
author_facet Rajshekhar A. Kore
Samir V. Jenkins
Azemat Jamshidi-Parsian
Alan J. Tackett
Robert J. Griffin
Srinivas Ayyadevara
Jawahar L. Mehta
author_sort Rajshekhar A. Kore
collection DOAJ
description 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 β-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.
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spelling doaj.art-9327d811ef5e44fa98721c9b972655512023-06-02T04:23:25ZengElsevierBiochemistry and Biophysics Reports2405-58082023-07-0134101463Proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by MSC exosomesRajshekhar A. Kore0Samir V. Jenkins1Azemat Jamshidi-Parsian2Alan J. Tackett3Robert J. Griffin4Srinivas Ayyadevara5Jawahar L. Mehta6Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Corresponding author.Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USADepartment of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USADepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USADepartment of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USADepartment of Geriatrics, Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USADivision of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Corresponding author.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 β-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.http://www.sciencedirect.com/science/article/pii/S2405580823000444Mesenchymal stem cell exosomesMyocardial ischemiaPost-ischemic fibrosisProteomicsTranscription factors
spellingShingle Rajshekhar A. Kore
Samir V. Jenkins
Azemat Jamshidi-Parsian
Alan J. Tackett
Robert J. Griffin
Srinivas Ayyadevara
Jawahar L. Mehta
Proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by MSC exosomes
Biochemistry and Biophysics Reports
Mesenchymal stem cell exosomes
Myocardial ischemia
Post-ischemic fibrosis
Proteomics
Transcription factors
title Proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by MSC exosomes
title_full Proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by MSC exosomes
title_fullStr Proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by MSC exosomes
title_full_unstemmed Proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by MSC exosomes
title_short Proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by MSC exosomes
title_sort proteomic analysis of transcription factors involved in the alteration of ischemic mouse heart as modulated by msc exosomes
topic Mesenchymal stem cell exosomes
Myocardial ischemia
Post-ischemic fibrosis
Proteomics
Transcription factors
url http://www.sciencedirect.com/science/article/pii/S2405580823000444
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