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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1393534
This article is part of the Research Topic Exploring Small Molecule Inhibitors in Cardiovascular and Cerebrovascular Diseases View all 6 articles
Transglutaminase 2 regulates endothelial cell calcification via IL-6-mediated autophagy
Provisionally accepted- 1 Zhengzhou Central Hospital, Zhengzhou, Henan Province, China
- 2 Zhengzhou University, Zhengzhou, Henan Province, China
- 3 Zhengzhou Second People's Hospital, Zhengzhou, Henan Province, China
Endothelial cell (EC) calcification is an important marker of atherosclerotic calcification. ECs play a critical role not only in atherogenesis but also in intimal calcification, as they have been postulated to serve as a source of osteoprogenitor cells that initiate this process. While the role of transglutaminase 2 (TG2) in cellular differentiation, survival, apoptosis, autophagy, and cell adhesion is well established, the mechanism underlying the TG2-mediated regulation of EC calcification is yet to be fully elucidated. While numerous studies have explored the regulation of autophagy by interleukin (IL)-6 in various cell types, the majority of these investigations have been limited to cancer cells. To gain a better understanding of the pathogenesis of atherosclerotic calcification, we employed human umbilical vein ECs (HUVECs) to establish an EC calcification model. Our findings demonstrated that TG2 promoted calcification in HUVECs, regulated the NF-κB signaling pathway, and induced IL-6 autocrine signaling in ECs, which serves as a downstream signaling molecule of NF-κB. Finally, the results demonstrated that IL-6 activated the JAK2/STAT3 signaling pathway to suppress autophagy in HUVECs, as shown by AZD-1480, a potent JAK2 inhibitor. In addition, IL-6 promoted calcification in HUVECs, which was inhibited after AZD-1480 treatment. Collectively, our results indicated that the TG2/NF-κB-IL-6-JAK2/STAT3 signaling axis mediated the regulation of EC calcification by modulating endothelial autophagy.
Keywords: transglutaminase 2, calcification, Autophagy, Interleukin-6, autocrine, Endothelial Cells
Received: 29 Feb 2024; Accepted: 31 Oct 2024.
Copyright: © 2024 Liu, Cai, Wang, Liu, Zhang, Zheng, Li, Li, Cui, Lv and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhiyuan Cai, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China
Yan Wang, Zhengzhou Second People's Hospital, Zhengzhou, 450005, Henan Province, China
Xinye Liu, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China
Bin Zhang, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China
Qian Zheng, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China
Jingye Li, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China
Cien Li, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China
Dongwei Yang, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China
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