Autophagy dysfunction may be involved in the pathogenesis of ankylosing spondylitis

Abstract

The present study aimed to investigate the expression and significance of the mRNA of genes associated with autophagy and long non-coding RNA (lncRNA) GAS5 in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS). The mRNA levels of microtubule-associated protein light chain 3 (LC3), Beclin1, autophagy-related gene (ATG)3, ATG5, ATG12, ATG 16 ligand 1 (ATG16L1) and lncRNA growth arrest-specific 5 (GAS5) in PBMCs from 60 patients with AS and 30 healthy controls (HC) were examined by reverse transcription-quantitative PCR. The correlations between the levels of LC3, Beclin1, ATG3, ATG5, ATG12 and ATG16L1 mRNA as well as lncRNA GAS5 levels with disease activity and laboratory parameters in patients with AS were determined by Spearman correlation analysis. In addition, the diagnostic value of lncRNA GAS5 for AS was explored through establishing a receiver operating characteristic (ROC) curve. The results indicated that, compared to the HCs, patients with AS had lower expression levels of LC3, ATG5, ATG12, ATG16L1 and lncRNA GAS5 in their PBMCs. Compared with those in patients with inactive AS, the levels of ATG5 and ATG12 were lower than those in patients with active AS. Of note, ATG5 and ATG12 mRNA levels were negatively correlated with disease activity indexes. lncRNA GAS5 was positively correlated with the expression of Beclin1, ATG3, ATG5, ATG12 and ATG16L1. The area under the ROC curve for the use of lncRNA GAS5 expression to diagnose AS was 0.808 with a 95% CI of 0.714-0.902. In conclusion, patients with AS had decreased expression of genes associated with autophagy and lncRNA GAS5. The extent of the reduction in ATG5 and ATG12 expression levels in patients with AS was correlated with the disease severity and activity. Furthermore, lncRNA GAS5 was a diagnostic indicator of AS.

Joint together: The etiology and pathogenesis of ankylosing spondylitis

“…In contrast, the findings from the team of Rik Lories support the downregulation of autophagy-related genes (ATG16L1, IRGM, HSP90AA1) in PB ( 161 ). Further research revealed autophagy dysfunction with the downregulation of MAP1LC3A and ATG5/12/16L1 in PBMCs, covering all markers used in the previous study ( 162 ). This dysfunction is attributed to a decrease in the autophagy mediator lncRNA GAS5.…”

Bioinformatics Analysis of the Molecular Mechanism and Potential Treatment Target of Ankylosing Spondylitis

“…For example, Li et al reported that the expression of lncRNA MEG 3 was downregulated in AS (19), which affected the length of the patient's hospital stay. Tan et al proposed that the pathogenesis of AS might be related to insufficient autophagy and downregulation of lncRNA GAS 5, and lncRNA GAS 5 might have clinical application value (20). Our discovery gives a new hint of uncovering the traits of AS and exploiting a prospective target for AS treatment.…”

New Insights into the Regulatory Role of Ferroptosis in Ankylosing Spondylitis via Consensus Clustering of Ferroptosis-Related Genes and Weighted Gene Co-Expression Network Analysis

“…SNHG16 is related to MAPK1 , which is one of the key genes in ferroptosis; SNHG16 is also involved in intracerebral hemorrhage [ 103 ]. GAS5 has been described in both an AS cross-sectional study and a ferroptosis-related bioinformatics study [ 104 , 105 ]. Because these non-coding RNAs are simultaneously associated with redox homeostasis and musculoskeletal disorders, they may be bridging molecules between ferroptosis and AS, and may, therefore, be possible therapeutic targets and tools in future research.…”