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Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling

Wenjuan Zhang, Bowei Zhou, Xiao Yang, Jin Zhao, Jingjuan Hu, Yuqi Ding, Shuteng Zhan, Yifeng Yang, Jun Chen, Fu Zhang, Bingcheng Zhao, Fan Deng, Zebin Lin, Qishun Sun, Fangling Zhang, Zhiwen Yao, Weifeng Liu, Cai Li () and Ke-Xuan Liu ()
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Wenjuan Zhang: Southern Medical University, Guangzhou
Bowei Zhou: Southern Medical University, Guangzhou
Xiao Yang: Southern Medical University, Guangzhou
Jin Zhao: Southern Medical University, Guangzhou
Jingjuan Hu: Southern Medical University, Guangzhou
Yuqi Ding: Southern Medical University, Guangzhou
Shuteng Zhan: Southern Medical University, Guangzhou
Yifeng Yang: Southern Medical University, Guangzhou
Jun Chen: Southern Medical University, Guangzhou
Fu Zhang: Southern Medical University, Guangzhou
Bingcheng Zhao: Southern Medical University, Guangzhou
Fan Deng: Southern Medical University, Guangzhou
Zebin Lin: Southern Medical University, Guangzhou
Qishun Sun: Southern Medical University, Guangzhou
Fangling Zhang: Southern Medical University, Guangzhou
Zhiwen Yao: Southern Medical University, Guangzhou
Weifeng Liu: Southern Medical University, Guangzhou
Cai Li: Southern Medical University, Guangzhou
Ke-Xuan Liu: Southern Medical University, Guangzhou

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Intestinal ischemia/reperfusion (I/R) injury is a severe clinical condition without optimal diagnostic markers nor clear molecular etiological insights. Plasma exosomal circular RNAs (circRNAs) are valuable biomarkers and therapeutic targets for various diseases, but their role in intestinal I/R injury remains unknown. Here we screen the expression profile of circRNAs in intestinal tissue exosomes collected from intestinal I/R mice and identify circEZH2_005 as a significantly downregulated exosomal circRNA. In parallel, circEZH2_005 is also reduced in the plasma of clinical cardiac surgery patients who developed postoperative intestinal I/R injury. Exosomal circEZH2_005 displays a significant diagnostic value for intestinal injury induced by I/R. Mechanistically, circEZH2_005 is highly expressed in intestinal crypt cells. CircEZH2_005 upregulation promotes the proliferation of Lgr5+ stem cells by direct interaction with hnRNPA1, and enhanced Gprc5a stability, thereby alleviating I/R-induced intestinal mucosal damage. Hence, exosomal circEZH2_005 may serve as a biomarker for intestinal I/R injury and targeting the circEZH2_005/hnRNPA1/Gprc5a axis may be a potential therapeutic strategy for intestinal I/R injury.

Date: 2023
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DOI: 10.1038/s41467-023-41147-3

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