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Molecular mechanisms of AMPK/YAP/NLRP3 signaling pathway affecting the occurrence and development of ankylosing spondylitis.
- Source :
- Journal of Orthopaedic Surgery & Research; 11/4/2023, Vol. 18 Issue 1, p1-22, 22p
- Publication Year :
- 2023
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- DISEASE progression
IN vitro studies
BIOLOGICAL models
INTERLEUKINS
IN vivo studies
BONE growth
FIBROBLASTS
ANKYLOSING spondylitis
AMP-activated protein kinases
YAP signaling proteins
INFLAMMATION
ANIMAL experimentation
SIGNAL peptides
CELLULAR signal transduction
MOLECULAR biology
NUCLEOTIDES
GENE expression
ENZYME-linked immunosorbent assay
DESCRIPTIVE statistics
TRANSCRIPTION factors
COMPUTED tomography
DATA analysis software
CARRIER proteins
PHOSPHORYLATION
MICE
CASPASES
Subjects
Details
- Language :
- English
- ISSN :
- 1749799X
- Volume :
- 18
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Orthopaedic Surgery & Research
- Publication Type :
- Academic Journal
- Accession number :
- 173431968
- Full Text :
- https://doi.org/10.1186/s13018-023-04200-x