Sinomenine inhibits fibroblast-like synoviocyte proliferation by regulating alpha 7nAChR expression via ERK/Egr-1 pathway
Sinomenine inhibits fibroblast-like synoviocyte proliferation by regulating alpha 7nAChR expression via ERK/Egr-1 pathway
复制标题
青藤碱通过 ERK/Egr-1 通路调节 α7nAChR 表达抑制成纤维样滑膜细胞增殖
DOI：
10.1016/j.intimp.2018.01.015
复制
发表时间：
2018
影响因子：
5.6
通讯作者：
Dong Yan
中科院分区：
文献类型：
--
作者：
Yi Lang;Lyn Yan jun;Peng Chong;Zhu Rui liu;Bai Sha sha;Liu Liang;Wang Pei xun;Zhou Hua;Dong Yan
Fibroblast like synoviocyte (FLS) is a crucial in the pathogenesis of rheumatoid arthritis (RA), and involved in inflammation and joint destruction. Sinomenine (SIN), an alkaloid derived from the plantSinomeniumacutum, has anti-inflammatory and analgesic effect and been used for RA treatment in China. Alpha 7 nicotinic acetylcholine receptors (α7nAChR), as the key receptor in cholinergic anti-inflammatory pathway (CAP) to inhibit inflammation, has been detected in RA patients synovium, but its role is still unclear. Here we investigated the association between the aggressive proliferation of FLS and α7nAChR expression and the effect of sinomenine. FLS was isolated from synovial tissues of adjuvant-induced-arthritis (AIA) rat. Tumor necrosis factor(TNF)-α was used to induce the aggressive proliferation of FLS. MTT assay was applied to evaluate the proliferation of FLS. The messenger RNA (mRNA) and protein levels of α7nAChR and early growth response gene-1 (Egr-1) were measured. The results showed that TNF-α induced FLS proliferation in vitro (P < .01) and increased the phosphorylation of ERK1/2 and the expression of Egr-1 and α7nAChR (P < .05 or P < .01). U0126, the inhibitor of ERK1/2 inhibited α7nAChR expression and FLS proliferation significantly (P < .05 or P < .01). Specific short interference RNA(siRNA) of α7nAChR decreased α7nAChR expression and inhibited FLS proliferation as well. SIN inhibited the proliferation of FLS and decreased the phosphorylation of ERK1/2, and the expression of Egr-1 and α7nAChR induced by TNF-α (P < .05). In conclusion, the expression of α7nAChR involved in the aggressive proliferation of FLS induced by TNF-α and was regulated by ERK/Egr-1 signal pathway. SIN inhibited FLS proliferation and α7nAChR expression through inhibiting ERK/Egr-1 signal pathway, this may contribute to the anti-inflammatory and anti-arthritic effect of SIN.
