iScience (Apr 2023)

Adiponectin-mediated promotion of CD44 suppresses diabetic vascular inflammatory effects

  • Yanru Duan,
  • Shihan Zhang,
  • Yuanyuan Xing,
  • Ye Wu,
  • Wen Zhao,
  • Pinxue Xie,
  • Huina Zhang,
  • Xinxiao Gao,
  • Yanwen Qin,
  • Yajing Wang,
  • Xinliang Ma,
  • Yunhui Du,
  • Huirong Liu

Journal volume & issue
Vol. 26, no. 4
p. 106428

Abstract

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Summary: While adiponectin (APN) was known to significantly abolish the diabetic endothelial inflammatory response, the specific mechanisms have yet to be elucidated. Aortic vascular tissues from mice fed normal and high-fat diets (HFD) were analyzed by transcriptome analysis. GO functional annotation showed that APN inhibited vascular endothelial inflammation in an APPL1-dependent manner. We confirmed that activation of the Wnt/β-catenin signaling plays a key role in APN-mediated anti-inflammation. Mechanistically, APN promoted APPL1/reptin complex formation and β-catenin nuclear translocation. Simultaneously, we identified APN promoted the expression of CD44 by activating TCF/LEF in an APPL1-mediated manner. Clinically, the serum levels of APN and CD44 were decreased in diabetes; the levels of these two proteins were positively correlated. Functionally, treatment with CD44 C-terminal polypeptides protected diabetes-induced vascular endothelial inflammation in vivo. Collectively, we provided a roadmap for APN-inhibited vascular inflammatory effects and CD44 might represent potential targets against the diabetic endothelial inflammatory effect.

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