GDF11 antagonizes TNF--induced inflammation and protects against the development of inflammatory arthritis in mice
GDF11 antagonizes TNF--induced inflammation and protects against the development of inflammatory arthritis in mice
复制标题
GDF11 拮抗 TNF-α 诱导的炎症并防止小鼠炎症性关节炎的发展
DOI：
10.1096/fj.201801375rr
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发表时间：
2019-03-01
期刊：
影响因子：
4.8
通讯作者：
Zhao, Yunpeng
中科院分区：
文献类型：
--
作者：
Li, Weiwei;Wang, Wenhan;Zhao, Yunpeng
生长分化因子11 （Growth differentiation factor 11, GDF11）是TGF-超家族的关键成员，在多种疾病中发挥着关键作用。最近，GDF11被发现抑制活化B细胞（NF-B）信号通路的核因子kappa-轻链增强子，并具有抗炎症作用。本研究旨在探讨GDF11在类风湿关节炎（RA）发展中的作用。我们证明了GDF11治疗可以拮抗巨噬细胞中TNF诱导的炎症。此外，在胶原诱导的关节炎和胶原抗体诱导的关节炎模型中，GDF11抑制关节炎的发展。通过腺相关病毒GDF11的局部基因转移发挥治疗作用，而GDF11的局部敲低会加重胶原诱导关节炎模型中的炎症，这可以通过炎症生物标志物的表达水平和关节结构的破坏来检测。此外，体外实验和荧光素酶报告基因小鼠实验的结果表明，NF-B途径可能在GDF11治疗RA的作用中起关键作用。本研究表明GDF11是治疗炎性关节炎（包括RA）的潜在靶点。W W。李,王,刘,L,瞿,R,陈,X。,邱,C。李,J。,Hayball, J。,刘,L,陈,J。,,X。,,X。,赵,y GDF11对抗肿瘤坏死因子,诱导炎症和防止小鼠炎性关节炎的发展。
Growth differentiation factor 11 (GDF11), a key member of the TGF- superfamily, plays critical roles in various medical conditions. Recently, GDF11 was found to suppress the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) signaling pathway and protect against inflammation. This study aimed to investigate the role of GDF11 in the development of rheumatoid arthritis (RA). We demonstrated that GDF11 treatment antagonized TNF--induced inflammation in macrophages. Moreover, GDF11 inhibited the development of arthritis in the collagen-induced arthritis and collagen antibody-induced arthritis models. Local gene transfer of GDF11 via adeno-associated virus exerted therapeutic effects, while local knockdown of GDF11 exaggerated inflammation in our collagen-induced arthritis model, as detected by expression levels of inflammatory biomarkers and the destruction of joint structures. Additionally, the results from both in vitro experiments and luciferase reporter gene mouse experiments implied that the NF-B pathway might play a critical role in the therapeutic effect of GDF11 in RA. This study presents GDF11 as a potential target for the treatment of inflammatory arthritis, including RA.Li, W., Wang, W., Liu, L., Qu, R., Chen, X., Qiu, C., Li, J., Hayball, J., Liu, L., Chen, J., Wang, X., Pan, X., Zhao, Y. GDF11 antagonizes TNF--induced inflammation and protects against the development of inflammatory arthritis in mice.