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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.
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참고문헌 (25)
참고문헌 신청
Aggarwal S / 2005 / Human mesenchymal stem cells modulate allogeneic immune cell responses / Blood 105 : 1815 ~ 1822
Bellot G / 2009 / Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains / Mol Cell Biol 29 : 2570 ~ 2581
Braun J / 2007 / Ankylosing spondylitis / Lancet 369 : 1379 ~ 1390
Brown MA / 1997 / Susceptibility to ankylosing spondylitis in twins the role of genes, HLA, and the environment / Arthritis Rheum 40 : 1823 ~ 1828
Caffrey MF / 1973 / Human lymphocyte antigen association in ankylosing spondylitis / Nature 242 : 121 ~
Bellot G / 2009 / Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains / Mol Cell Biol 29 : 2570 ~ 2581
Braun J / 2007 / Ankylosing spondylitis / Lancet 369 : 1379 ~ 1390
Brown MA / 1997 / Susceptibility to ankylosing spondylitis in twins the role of genes, HLA, and the environment / Arthritis Rheum 40 : 1823 ~ 1828
Caffrey MF / 1973 / Human lymphocyte antigen association in ankylosing spondylitis / Nature 242 : 121 ~
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