Triptolide promotes the apoptosis and attenuates the inflammation of fibroblast‐like synoviocytes in rheumatoid arthritis by down‐regulating lncRNA ENST00000619282

Abstract

Rheumatoid arthritis (RA), recognized as a common chronic autoimmune disease, is characterized by the excessive proliferation and inflammatory infiltration of fibroblast‐like synoviocytes (FLS). In this study, our purpose is to elucidate the mechanisms of triptolide (TPL) in the treatment of RA by regulating the long non‐coding RNA (lncRNA) ENST00000619282, which promoted apoptosis and reduced inflammatory infiltration of FLS in RA (RA‐FLS). RA‐FLS was treated with different concentrations of TPL at different time points. CCK‐8 assay, ELISA, RT‐qPCR, immunofluorescence, TUNEL assay, and the transmission electron microscopy were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Next, the involvement of ENST00000619282 in TPL‐mediated protection against RA was explored. ENST00000619282 expression was significantly increased in the peripheral blood mononuclear cells (PBMCs) of RA patients. ENST0000061928 expression in RA PBMCs was positively associated with ESR, RF, CCP, and DAS28, while TPL treatment led to a downregulation of ENST00000619282. In addition, ENST00000619282 was significantly increased in RA‐FLS. Furthermore, overexpression of ENST00000619282 elevated the levels of pro‐apoptotic and pro‐inflammatory factors, while reduced the levels of anti‐apoptotic proteins and antiinflammatory factors. Besides, TPL treatment could reverse these effects by ENST00000619282 overexpression. The anti‐RA potential of TPL might be achieved by downregulating ENST00000619282, thereby promoting apoptosis, and reducing the inflammatory response in RA.

Overexpression of long noncoding RNA LINC00638 inhibits inflammation and oxidative stress in rheumatoid arthritis fibroblast‐like synoviocytes by regulating the Nrf2/HO‐1 pathway

“…The immortalized cell line of RA‐FLS was obtained by using lentivirus vector‐mediated SV40+ T antigen transfection. 17 The second generation of the cells was used for identification, and the level of Vimentin protein was identified by immunofluorescence (IF) cytochemistry. RA‐FLS were thereafter fixed by paraformaldehyde and incubated with Triton X‐100 for 0.5 h. The primary anti‐vimentin (Bs‐8533R; Bioss) was then added and incubated at 4°C for 8 h. The secondary antibody (1:400, goat anti‐rabbit) was then added to all the sections and incubated for 1 h. After DAPI staining, the tablets were sealed and observed under a fluorescence microscope (BA410E; Motic).…”

Natural medicines of targeted rheumatoid arthritis and its action mechanism

“…In the research by Wen et al. ( 95 ), the overexpression of ENST 000060619282 increases the levels of pro-apoptotic and pro-inflammatory factors, and reduces the levels of anti-apoptotic proteins and anti-inflammatory factors at the same time. However, the mechanism of triptolide in promoting the apoptosis of RA-FLS cells and reducing the inflammatory response may be achieved by down-regulating ENST 00000619282 (lnc RNA).…”

LncRNAs and Rheumatoid Arthritis: From Identifying Mechanisms to Clinical Investigation

“…LINC00152/NF-kB feedback loop promotes RAFLS inflammation via regulating miR-103a/TAK1 axis and YY1 expression. (20) and reduce joint inflammation of FLSs in RA (41). Astragaloside (AST) can reduce the expression level of LncRNA LOC100912373 in FLSs, and offset the proliferation of FLSs by LOC100912373 (52).…”

“…The expression of ENST0000061928 in the PBMC of RA patients correlates positively with the expression of RF. The down-regulation of the LncRNA ENST0000061928 can reduce the expression of RF in RA ( 41 ). Similarly, LncRNA HIX003209 has also been reported to be upregulated in RA and positively correlated with RF levels ( 15 ).…”

“…For example, triptolide (TPL) can downregulate the expression of LncRNA ENST00000619282, promote apoptosis and reduce joint inflammation of FLSs in RA ( 41 ). Astragaloside (AST) can reduce the expression level of LncRNA LOC100912373 in FLSs, and offset the proliferation of FLSs by LOC100912373 ( 52 ).…”