期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2022, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2022/6776050
关键词
-
类别
资金
- National Natural Science Foundation of China
- Science and Technology Program of Guangzhou
- Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory
- Youth Science and Technology Innovation Talent Program of Guangdong TeZhi Plan
- Guangdong Local Innovation Team Program
- [81770386]
- [82070403]
- [81973388]
- [81973235]
- [201804010086]
- [2021A0505030031]
- [2018GZR110105001]
- [2019TQ05Y136]
- [2019BT02Y262]
This study discovered that a specific piericidin diglycoside, S18, can suppress inflammatory responses and alleviate aortic valve lesions in a CAVD model. S18 binds directly to IL-37 to alleviate inflammatory responses in HAVICs. These findings suggest that S18 has the potential to be a therapeutic agent for preventing CAVD development.
Calcific aortic valve disease (CAVD) is a valvular disease frequently in the elderly individuals that can lead to the valve dysfunction. Osteoblastic differentiation of human aortic valve interstitial cells (HAVICs) induced by inflammation play a crucial role in CAVD pathophysiological processes. To date, no effective drugs for CAVD have been established, and new agents are urgently needed. Piericidin glycosides, obtained from a marine-derived Streptomyces strain, were revealed to have regulatory effects on mitochondria in previous studies. Here, we discovered that 13-hydroxypiericidin A 10-O-alpha-D-glucose (1 -> 6)-beta-D-glucoside (S18), a specific piericidin diglycoside, suppresses lipopolysaccharide- (LPS) induced inflammatory responses of HAVICs by alleviating mitochondrial stress in an interleukin (IL)-37-dependent manner. Knockdown of IL-37 by siRNA not only exaggerated LPS-induced HAVIC inflammation and mitochondrial stress but also abrogated the anti-inflammatory effect of S18 on HAVICs. Moreover, S18 alleviated aortic valve lesions in IL-37 transgenic mice of CAVD model. Microscale thermophoresis (MST) and docking analysis of five piericidin analogues suggested that diglycosides, but not monoglycosides, exert obvious IL-37-binding activity. These results indicate that S18 directly binds to IL-37 to alleviate inflammatory responses in HAVICs and aortic valve lesions in mice. Piericidin diglycoside S18 is a potential therapeutic agent to prevent the development of CAVD.
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