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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Z, 2023. "Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41147-3
    DOI: 10.1038/s41467-023-41147-3
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