Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients.

Abstract

Ankylosing spondylitis (AS) is a type of autoimmune disease that predominantly affects the spine and sacroiliac joints. However, the pathogenesis of AS remains unclear. Some evidence indicates that infection with bacteria, especially Gram-negative bacteria, may have an important role in the onset and progression of AS. Recently, many studies have demonstrated that mesenchymal stem cells (MSCs) dysfunction may contribute to the pathogenesis of many rheumatic diseases. We previously demonstrated that MSCs from AS patients exhibited markedly enhanced osteogenic differentiation capacity in vitro under non-inflammatory conditions. However, the properties of MSCs from AS patients in an inflammatory environment have never been explored. Lipopolysaccharide (LPS), a proinflammatory substance derived from the outer membrane of Gram-negative bacteria, can alter the status and function of MSCs. However, whether MSCs from AS patients exhibit abnormal responses to LPS stimulation has not been reported. Autophagy is a lysosome-mediated catabolic process that participates in many physiological and pathological processes. The link between autophagy and AS remains largely unknown. The level of autophagy in ASMSCs after LPS stimulation remains to be addressed. In this study, we demonstrated that although the basal level of autophagy did not differ between MSCs from healthy donors (HDMSCs) and ASMSCs, LPS-induced autophagy was weaker in ASMSCs than in HDMSCs. Specifically, increased TRAF4 expression in ASMSCs impaired LPS-induced autophagy, potentially by inhibiting the phosphorylation of Beclin-1. These data may provide further insight into ASMSC dysfunction and the precise mechanism underlying the pathogenesis of AS.

• Authors: Jinteng Li, Peng Wang, Zhongyu Xie, Rui Yang, Yuxi Li, Xiaohua Wu, Hongjun Su, Wen Deng, Shan Wang, Zhenhua Liu, Shuizhong Cen, Yi Ouyang, Yanfeng Wu, Huiyong Shen
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 49 Issue 6 Pg. e343 (06 09 2017) ISSN: 2092-6413 [Electronic] United States
• PMID: 28604663 (Publication Type: Journal Article)

Chemical References

• Autophagy-Related Proteins
• Beclin-1
• Lipopolysaccharides
• TNF Receptor-Associated Factor 4
• TRAF4 protein, human

Topics

• Adult
• Autophagy (drug effects)
• Autophagy-Related Proteins (genetics)
• Beclin-1 (metabolism)
• Chronic Disease
• Female
• Humans
• Lipopolysaccharides (pharmacology)
• Male
• Mesenchymal Stem Cells (drug effects, metabolism)
• Osteogenesis
• Phosphorylation
• Primary Cell Culture
• Spondylitis, Ankylosing (metabolism, pathology)
• TNF Receptor-Associated Factor 4 (genetics, metabolism)