RETRACTED: Marine-Derived Piericidin Diglycoside S18 Alleviates Inflammatory Responses in the Aortic Valve via Interaction with Interleukin 37 (Retracted Article)

作者：Li, Shunyi; She, Jianglian; Zeng, Jingxin; Xie, Kaiji; Luo, Zichao; Su, Shuwen; Chen, Jun; Xian, Gaopeng; Cheng, Zhendong; Zhao, Jing; Li, Shaoping; Xu, Xingbo; Xu, Dingli^*; Tang, Lan^*; Zhou, Xuefeng^*; Zeng, Qingchun^*

来源：Oxidative Medicine and Cellular Longevity, 2022, 2022: 6776050.

DOI：10.1155/2022/6776050

• INTERSTITIAL-CELLS
• EXPRESSION
• SUPPRESSES
• DISEASE
• CALCIFICATION
• DYSFUNCTION
• MECHANISMS
• MODELS
• DAMAGE
• IL-37

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.

• 单位
  中国科学院; 南方医科大学