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TGF-β3/Smad3 Contributes to Isoflurane Postconditioning Against Cerebral Ischemia–Reperfusion Injury by Upregulating MEF2C

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Abstract

Isoflurane postconditioning alleviates cerebral ischemic–reperfusion injury (CIRI), but the underlying mechanism has not been fully clarified. We previously demonstrated that the transforming growth factor beta-1 (TGF-β1)/Smads signaling pathway is involved in the neuroprotective effect of isoflurane postconditioning. TGF-β3 has a highly homologous sequence relative to that of TGF-β1. In this study, we explored the roles of the TGF-β3/Smad3 signaling pathway and myocyte enhancer factor 2C (MEF2C) in neuroprotection induced by isoflurane postconditioning. A CIRI rat model was established by middle cerebral artery occlusion for 1.5 h, followed by 24 h of reperfusion. Isoflurane postconditioning led to lower infarct volumes and neurologic deficit scores, more surviving neurons, and less damaged and apoptotic neurons as compared with those of CIRI rats. Moreover, isoflurane postconditioning upregulated the expressions of TGF-β3, p-Smad3, and MEF2C. However, the neuroprotective effect was reversed by pirfenidone, a TGF-β3/Smad3 signaling pathway inhibitor. Also, pirfenidone treatment downregulated the expression of MEF2C. These results indicate that the TGF-β3/Smad3 signaling pathway contributes to the neuroprotection of isoflurane postconditioning after CIRI and is possibly related to MEF2C.

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Funding

This study was supported by the Natural Science Foundation of China (Grant Nos. 81860249, 81860209). This study was performed at the Key Laboratory of Xinjiang Endemic and Ethnic Diseases in the Xinjiang Provincial Department of Physiology, School of Medicine, Shihezi University.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Shihezi University and the Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi, 832002, China

    Yuqi Yang, Long Chen, Junqiang Si & Ketao Ma

  2. Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihe Zi University, Shihezi, 832002, China

    Jiangwen Yin & Yan Li

  3. Department of Anesthesiology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China

    Chengwei Yang & Sheng Wang

Authors
  1. Yuqi Yang
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  2. Long Chen
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  3. Junqiang Si
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  4. Ketao Ma
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  5. Jiangwen Yin
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  6. Yan Li
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  7. Chengwei Yang
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  8. Sheng Wang
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Contributions

YY conceived and designed the study. YY and LC performed the experiments. YY analyzed the data and finished the essay. SW and CY contributed to revising the manuscript. JS and KM coordinated and directed the project. JY and YL participated in guiding the revision of articles. All authors read and approved the final manuscript.

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Correspondence to Sheng Wang.

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The authors have no potential conflicts of interest to declare.

Ethical Approval

The protocol was approved by the Animal Care and Use Committee of the First Affiliated Hospital of the Medical College at Shihezi University and was conducted in strict accordance with the guidelines of the Guide for the Care and Use of Laboratory Rats.

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This study is not involved in human participants so that there is no informed consent.

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Yuqi Yang and Long Chen are the co-first authors.

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Yang, Y., Chen, L., Si, J. et al. TGF-β3/Smad3 Contributes to Isoflurane Postconditioning Against Cerebral Ischemia–Reperfusion Injury by Upregulating MEF2C. Cell Mol Neurobiol 40, 1353–1365 (2020). https://doi.org/10.1007/s10571-020-00822-5

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  • DOI: https://doi.org/10.1007/s10571-020-00822-5

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