Ubiquitylation of MFHAS1 by the ubiquitin ligase praja2 promotes M1 macrophage polarization by activating JNK and p38 pathways.
Ubiquitylation of MFHAS1 by the ubiquitin ligase praja2 promotes M1 macrophage polarization by activating JNK and p38 pathways.
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泛素连接酶 praja2 对 MFHAS1 的泛素化通过激活 JNK 和 p38 途径促进 M1 巨噬细胞极化
DOI：
10.1038/cddis.2017.102
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发表时间：
2017-05-04
影响因子：
9
通讯作者：
Miao C
中科院分区：
文献类型：
--
作者：
Zhong J;Wang H;Chen W;Sun Z;Chen J;Xu Y;Weng M;Shi Q;Ma D;Miao C
脓毒症是一种由感染引起的全身性炎症。M1 - M2巨噬细胞极化之间的平衡在脓毒症的发病机制中起着至关重要的作用。然而，巨噬细胞极化的确切机制尚不清楚。我们先前发现，与非脓毒症患者相比，脓毒症患者的恶性纤维组织细胞瘤扩增序列1（MFHAS1）水平显著升高，并且参与了Toll样受体（TLR）2/c - Jun N末端激酶（JNK）/核因子（NF）-κB通路的激活。在本研究中，我们探讨了MFHAS1是否参与巨噬细胞极化，并确定了MFHAS1对炎症的影响。我们进行了体外下拉实验和体内免疫共沉淀实验，发现E3泛素连接酶praja2可直接与MFHAS1结合。原位免疫染色分析证实了内源性praja2与MFHAS1的共定位。我们首次报道praja2促进泛素化MFHAS1的积累但不降解它。此外，我们的结果表明，praja2对MFHAS1的泛素化正向调节TLR2介导的JNK/p38通路，促进M1巨噬细胞极化、M2向M1巨噬细胞转化以及炎症。
Sepsis is a systemic inflammation caused by infection. The balance between M1–M2 macrophage polarization has an essential role in the pathogenesis of sepsis. However, the exact mechanism underlying macrophage polarization is unclear. We previously showed that levels of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) were significantly elevated in septic patients compared with those in nonseptic patients, and involved in the activation of Toll-like receptor (TLR) 2/c-Jun N-terminal kinase (JNK)/nuclear factor (NF)-κB pathway. In the present study, we explored whether MFHAS1 was involved in macrophage polarization and determined the effect of MFHAS1 on inflammation. We performed in vitro pulldown assays and in vivo co-immunoprecipitation assays and found that E3 ubiquitin ligase praja2 could directly bind to MFHAS1. In situ immunostaining analysis confirmed the colocalization of endogenous praja2 with MFHAS1. We first reported that praja2 promotes the accumulation of ubiquitylated MFHAS1 but does not degrade it. Moreover, our results indicate that MFHAS1 ubiquitylation by praja2 positively regulates TLR2-mediated JNK/p38 pathway and promotes M1 macrophage polarization, M2 to M1 macrophage transformation and inflammation.
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影响因子：
4.8
作者：
Murphy, Michael;Xiong, Yanbao;Medvedev, Andrei E.
通讯作者：
Medvedev, Andrei E.
影响因子：
7.7
作者：
Abe T;Hirasaka K;Kagawa S;Kohno S;Ochi A;Utsunomiya K;Sakai A;Ohno A;Teshima-Kondo S;Okumura Y;Oarada M;Maekawa Y;Terao J;Mills EM;Nikawa T
通讯作者：
Nikawa T
影响因子：
8.7
作者：
Medvedev AE;Murphy M;Zhou H;Li X
通讯作者：
Li X
DOI：
10.1111/febs.12593
发表时间：
2014-01
期刊：
The FEBS journal
影响因子：
--
作者：
Dihanich S;Civiero L;Manzoni C;Mamais A;Bandopadhyay R;Greggio E;Lewis PA
通讯作者：
Lewis PA
M1和M2巨噬细胞：鸡肉和免疫力。
影响因子：
5.3
作者：
Mills CD;Ley K
通讯作者：
Ley K