FGF21 overexpression alleviates VSMC senescence in diabetic mice by modulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway

Yanyan Heng, Wei Wei, Linzhong Cheng, Feifei Wu, Haoyu Dong, Jingxia Li, Jianing Fu, Bingjie Yang, Xinyue Liang, Chunyan Liu, Haiju Li, Haihua Liu, and Pengfei Zhang

Fibroblast growth factor 21 (FGF21) is an endocrine factor that regulates glucose and lipid metabolism, improves insulin sensitivity, and has potential therapeutic effects in treating type 2 diabetes and non-alcoholic fatty liver disease. Recently, the pharmacological effects of FGF21 on vascular diseases have been increasingly recognized. This study elucidates the potential mechanism by which FGF21 mitigates vascular senescence accelerated by the diabetic environment through inhibiting the activation of inflammasome. FGF21 protects PPARγ function by inhibiting SYK-NLRP3 inflammasome pathway, maintains the level of catalase, counteracts the excess production of hydrogen peroxide within vascular smooth muscle cells (VSMCs) in a high-glucose environment, and alleviates VSMC senescence. Our research may propose a new relationship between inflammation and oxidative stress, elucidating novel mechanisms of FGF21's anti-inflammatory and antioxidant effects. In the cover story, a construction vehicle (FGF21) is depicted clearing hydrogen peroxide (red obstacles) formed from excess glucose (hexagons) on the road (blood vessels).

This cover is designed by Yinxi Zhou and Jianfeng Jin from Hainan Medical University.