1. Molecular mechanisms of AMPK/YAP/NLRP3 signaling pathway affecting the occurrence and development of ankylosing spondylitis
- Author
-
Ruiyang Fu, Xiaoqing Guo, Zhongqiang Pan, Yaling Wang, Jing Xu, Lei Zhang, and Jinxia Li
- Subjects
Ankylosing spondylitis ,AMPK ,Phosphorylation activation ,YAP ,NLRP3 ,Ubiquitination degradation ,Orthopedic surgery ,RD701-811 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Investigate the AMPK (protein kinase AMP-activated catalytic subunit alpha 1)/YAP (Yes1 associated transcriptional regulator)/NLRP3 (NLR family pyrin domain containing 3) signaling pathway's role in ankylosing spondylitis (AS) development using public database analysis, in vitro and in vivo experiments. Methods Retrieve AS dataset, analyze differential gene expression in R, conduct functional enrichment analysis, collect 30 AS patient and 30 normal control samples, and construct a mouse model. ELISA, IP, and knockdown experiments were performed to detect expression changes. Results NLRP3 was identified as a significant AS-related gene. Caspase-1, IL-1β, IL-17A, IL-18, IL-23, YAP, and NLRP3 were upregulated in AS patients. Overexpressing AMPK inhibited YAP's blockade on NLRP3 ubiquitination, reducing ossification in fibroblasts. Inhibiting AMPK exacerbated AS symptoms in AS mice. Conclusion AMPK may suppress YAP expression, leading to NLRP3 inflammasome inhibition and AS alleviation.
- Published
- 2023
- Full Text
- View/download PDF