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.
Duan, Yanru; Zhang, Shihan; Xing, Yuanyuan; Wu, Ye; Zhao, Wen; Xie, Pinxue; Zhang, Huina; Gao, Xinxiao; Qin, Yanwen; Wang, Yajing; Ma, Xin-Liang; Du, Yunhui; and Liu, Huirong, "Adiponectin-Mediated Promotion of CD44 Suppresses Diabetic Vascular Inflammatory Effects" (2023). Department of Emergency Medicine Faculty Papers. Paper 221.
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This article is the author's final published version in iScience, Volume 26, Issue 4, 2023, Article number 106428.
The published version is available at https://doi.org/10.1016/j.isci.2023.106428.
Copyright © 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).