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Serum Exosomal microRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ

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Abstract

Acute cerebral infarction (ACI) possesses high mortality. Exosomes present in serum have potential application value in ACI diagnosis. This study investigated the mechanism of serum exosomes in ACI. Serum exosomes isolated from ACI patients and normal people were identified and then injected into the established middle cerebral artery occlusion (MCAO) rat model to evaluate cerebral injury and inflammation. Exosomal microRNA (miR)-27-3p expression was detected and interfered to analyze rat cerebral inflammation. The binding relationship between miR-27-3p and PPARγ was predicted and verified. The lipopolysaccharide (LPS)-treated microglia model was established and intervened with miR-27-3p to detect PPARγ, Iba-1, and inflammation-related factor expressions. After overexpressing PPARγ, rat cerebral inflammation was evaluated. The clinical significance of serum exosomal miR-27-3p in ACI was evaluated. Serum exosomes from ACI patients caused exacerbated MCAO rat cerebral injury and poor behavior recovery, as well as promoted cerebral inflammation. Serum exosomal miR-27-3p deepened rat brain inflammation. miR-27-3p targeted PPARγ to promote microglia activation and inflammation-related factor expressions in MCAO rats, and overexpressing PPARγ attenuated MCAO rat cerebral inflammation. Serum exosomal miR-27-3p promised to be a biomarker for ACI. We proved that serum exosomes from ACI patients aggravated ACI patient cerebral inflammation via the miR-27-3p/PPARγ axis.

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Data Availability

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

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Funding

This study was supported by Jiaojiang District Science and Technology Project, Taizhou City, Zhejiang Province, China (172044) and the Youth Science and Technology Project of the Affiliated Municipal Hospital of the Medical College of Taizhou University (project no. TZMH-17-13).

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Authors and Affiliations

  1. Department of Neurology, Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, 318000, Zhejiang Province, China

    Zhinan Ye, Hao Xu, Bin Sun & Yaping Zhang

  2. Department of Anesthesiology, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, 323000, Zhejiang Province, China

    Jingchun Hu

  3. Department of Neurosurgery, Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, 318000, Zhejiang Province, China

    Yong Jin

  4. Department of Neurology, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, No.289 Kuocang Road, Liandu District of Lishui City, Wenzhou, 323000, Zhejiang Province, China

    Jianli Zhang

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  1. Zhinan Ye
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Contributions

Zhinan Ye and Jingchun Hu made substantial contributions to the conception of the present study. Hao Xu, Bin Sun, and Yong Jin performed the experiments and wrote the manuscript; Yaping Zhang and Jianli Zhang contributed to the design of the present study and interpreted the data. All authors read and approved the final version of the manuscript for publication.

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Correspondence to Jianli Zhang.

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All animal experiments were approved by the Ethics Committee of The Fifth Affiliated Hospital of Wenzhou Medical University. Significant efforts were made to minimize both the number of animals and their suffering. All procedures were strictly conducted in accordance with the code of ethics.

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Ye, Z., Hu, J., Xu, H. et al. Serum Exosomal microRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ. Inflammation 44, 1035–1048 (2021). https://doi.org/10.1007/s10753-020-01399-3

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