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

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.
AuthorsZhinan Ye, Jingchun Hu, Hao Xu, Bin Sun, Yong Jin, Yaping Zhang, Jianli Zhang
JournalInflammation (Inflammation) Vol. 44 Issue 3 Pg. 1035-1048 (Jun 2021) ISSN: 1573-2576 [Electronic] United States
PMID33394189 (Publication Type: Journal Article)
Chemical References
  • Inflammation Mediators
  • MIRN27 microRNA, human
  • MIRN27 microRNA, rat
  • MicroRNAs
  • PPAR gamma
  • PPAR gamma, rat
  • PPARG protein, human
Topics
  • Aged
  • Animals
  • Behavior, Animal
  • Brain (metabolism, pathology)
  • Case-Control Studies
  • Cell Line
  • Cerebral Infarction (blood, diagnostic imaging, genetics)
  • Databases, Genetic
  • Disease Models, Animal
  • Exosomes (genetics, metabolism, transplantation)
  • Female
  • Humans
  • Infarction, Middle Cerebral Artery (blood, genetics, metabolism, pathology)
  • Inflammation Mediators (metabolism)
  • Male
  • MicroRNAs (blood, genetics, metabolism)
  • Microglia (metabolism, pathology)
  • Middle Aged
  • PPAR gamma (genetics, metabolism)
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Rats

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