GDF11 Antagonizes Psoriasis-like Skin Inflammation via Suppression of NF-B Signaling Pathway
GDF11 Antagonizes Psoriasis-like Skin Inflammation via Suppression of NF-B Signaling Pathway
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GDF11 通过抑制 NF-kappaB 信号通路对抗银屑病样皮肤炎症
DOI：
10.1007/s10753-018-0895-3
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发表时间：
2019-02-01
期刊：
影响因子：
5.1
通讯作者：
Zhao, Yunpeng
中科院分区：
文献类型：
--
作者：
Wang, Wenhan;Qu, Ruize;Zhao, Yunpeng
生长分化因子-11 （Growth differentiation factor-11, GDF11）是转化生长因子（TGF-）超家族的关键成员，在正常生理过程和病理生理过程中都起着重要作用。最近，有报道称GDF11与几种炎症密切相关，并能防止炎症的发生。牛皮癣样皮肤炎症是一种常见的皮肤炎症性疾病，但其潜在机制尚不清楚。在本研究中，我们研究了GDF11在两种牛皮癣样皮肤炎症小鼠模型和肿瘤坏死因子- (TNF-)诱导的RAW264.7巨噬细胞中的表达模式。进一步培养RAW264.7细胞，GDF11在体外可拮抗TNF-的炎症功能。建立吡喹莫德诱导小鼠模型和il -23诱导小鼠模型，研究GDF11在体内的抗炎作用。结果，GDF11显著减轻了两种小鼠模型中皮肤炎症的严重程度。此外，核NF-B（活化B细胞的核因子-轻链增强子）信号通路的激活被GDF11抑制。总之，GDF11可能是预防和治疗牛皮癣样皮肤炎症的一个有希望的分子靶点。
Growth differentiation factor-11 (GDF11) is a key member of the transforming growth factor (TGF-) superfamily, which plays a momentous role in both normal physiological processes and pathophysiology processes. Recently, it was reported that GDF11 was closely associated with several inflammatory conditions and protected against development of inflammation. Psoriasis-like skin inflammation is a common skin inflammatory disease, yet much is unknown about the underlying mechanisms. In this study, we investigated the expression pattern of GDF11 in two psoriasis-like skin inflammation mice models and tumor necrosis factor- (TNF-)-induced RAW264.7 macrophages. Furthermore, RAW264.7 cell was cultured, and GDF11 antagonized the inflammatory function of TNF- in vitro. Moreover, imiquimod-induced mice model and IL-23-induced mice model were established to investigate the anti-inflammatory role of GDF11 in vivo. As a result, the administration of GDF11 remarkably attenuated the severity of skin inflammation in both two mice models. Additionally, the activation of nuclear NF-B (nuclear factor -light-chain-enhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation.