Molecular mechanisms of AMPK/YAP/NLRP3 signaling pathway affecting the occurrence and development of ankylosing spondylitis

  • J Orthop Surg Res. 2023 Nov 4;18(1):831. doi: 10.1186/s13018-023-04200-x.
Ruiyang Fu  1 ,  Xiaoqing Guo  1 ,  Zhongqiang Pan  1 ,  Yaling Wang  1 ,  Jing Xu  1 ,  Lei Zhang  1 ,  Jinxia Li  2
Affiliations
  • 1. Department of Acupuncture and Tuina, Huzhou Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang Chinese Medical University, Huzhou, 313000, Zhejiang Province, People's Republic of China.
  • 2. Department of Acupuncture and Tuina, Huzhou Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang Chinese Medical University, Huzhou, 313000, Zhejiang Province, People's Republic of China. [email protected].
PMID: 37925428 DOI: 10.1186/s13018-023-04200-x
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.

Keywords
AMPK; Ankylosing spondylitis; NLRP3; Phosphorylation activation; Ubiquitination degradation; YAP.
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