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Intractable Rare Dis Res. 2020 Feb;9(1):23-29. doi: 10.5582/irdr.2019.01139.

TXNDC5 protects synovial fibroblasts of rheumatoid arthritis from the detrimental effects of endoplasmic reticulum stress.

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School of Medicine and Life Sciences, University of Ji'nan-Shandong Academy of Medical Sciences, Ji'nan, Shandong, China.
Department of Orthopedics, Dezhou People's Hospital, Dezhou, Shandong, China.
Graduate Education Centre of the Shandong Academy of Medical Sciences, Ji'nan, Shandong, China.
Shandong Medicinal Biotechnology Centre, Key Laboratory for Rare and Uncommon Diseases of Shandong Province, Key Lab for Biotechnology Drugs of the Ministry of Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan, Shandong, China.
College of Clinical Medicine, Shandong University, Ji'nan, Shandong, China.


TXNDC5 is an endoplasmic reticulum (ER)-resident chaperone that protects the endothelium from secondary effects of ER stress. Previous studies by the current authors identified TXNDC5 as a key pathological factor in promoting the inflammatory phenotype of fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA). However, its activity in RA FLSs under ER stress remains unclear. The current study found that TXNDC5 is responsive to ER stress in RA FLSs since its expression was induced by ER stress at both the endogenous and secretory level. A functional study indicated that silencing TXNDC5 reduced the viability of RA FLSs more markedly in the presence of ER stressors. In contrast, rhTXNDC5 attenuated a decrease in cell viability as a result of ER stress. Moreover, silencing TXNDC5 attenuated the induction of IL-6 and IL-8 from RA FLSs in response to ER stress. In addition, rhTXNDC5 induced a greater increase in VEGF production during ER stress. These findings confirm the pro-survival and pro-inflammation roles of TXNDC5 under ER stress in RA FLSs. TXNDC5 appears to act as a mediator linking ER stress and inflammation of RA.


TXNDC5; endoplasmic reticulum stress; rheumatoid arthritis

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