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PPARγ Regulates Macrophage Polarization by Inhibiting the JAK/STAT Pathway and Attenuates Myocardial Ischemia/Reperfusion Injury In Vivo

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Abstract

This study aimed to investigate the role of PPARγ and underlying mechanisms in myocardial ischemia/reperfusion injury (IRI). IRI was surgically induced in mice and neonatal rat cardiomyocytes (NRCM) were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Quantitative genetic analysis and western blotting were performed to assess mRNA and protein levels, respectively, of PPARγ, as well as of different inflammatory, fibrosis, and apoptosis markers in cells and tissues. PPARγ was overexpressed in the heart of mice and NRCMs by viral transfection. Apoptosis and fibrosis were detected by TUNEL and Masson’s trichrome staining, respectively. Enzyme-linked immunosorbent assay was performed to detect M1 and M2 macrophage-related inflammatory factors present in mouse sera. PPARγ overexpression significantly inhibited OGD/R- and IRI-induced cardiomyocyte apoptosis and fibrosis in vitro and in vivo. Moreover, PPARγ overexpression inhibited IRI-induced secretion of M1-related proinflammatory factors, whereas it supported the secretion of M2-related anti-inflammatory factors. Notably, these events were found to be mediated by the JAK/STAT pathway. In conclusion, PPARγ regulates macrophage polarization upon IRI via the JAK/STAT pathway, which will in turn prevent myocardial apoptosis and fibrosis. Hence, PPARγ may represent a valuable target for myocardial IRI treatment.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

IL:

interleukin

IRI:

ischemia/reperfusion injury

NRCM:

neonatal rat cardiomyocyte

OGD/R:

oxygen-glucose deprivation and reoxygenation

PPAR:

peroxisome proliferator-activated receptor

RT-qPCR:

Real-time quantitative polymerase chain reaction

TGF:

transforming growth factor.

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Funding

This work was supported by the Startup Fund for Scientific Research, Fujian Medical University (Grant number: 2021QH1125) and the Research Project of Young and Middle-aged Teachers of Fujian Provincial Department of Education (Grant number: No. JAT200111).

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Authors and Affiliations

  1. Department of Cardiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou City, 362000, Fujian, China

    Shengnan Wang, Yinlian Cai, Rongsheng Bu, Yaoguo Wang & Chunchun Wu

  2. Department of Clinical Medicine, Quanzhou Medical College, Quanzhou City, 362000, Fujian, China

    Qingfan Lin & Youfang Chen

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  1. Shengnan Wang
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  2. Yinlian Cai
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  3. Rongsheng Bu
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  4. Yaoguo Wang
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  5. Qingfan Lin
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  7. Chunchun Wu
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Contributions

S.W. performed the experiments and data analysis. Y.C. and R.B. conceived and designed the study. Y.W. and Q.L. made the acquisition of data. Y.C. and C.W. found resources required. All authors read and approved the manuscript.

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Correspondence to Chunchun Wu.

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Wang, S., Cai, Y., Bu, R. et al. PPARγ Regulates Macrophage Polarization by Inhibiting the JAK/STAT Pathway and Attenuates Myocardial Ischemia/Reperfusion Injury In Vivo. Cell Biochem Biophys 81, 349–358 (2023). https://doi.org/10.1007/s12013-023-01137-0

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