Neddylation of EphB1 Regulates Its Activity and Associates with Liver Fibrosis.
Neddylation of EphB1 Regulates Its Activity and Associates with Liver Fibrosis.
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DOI：
10.3390/ijms24043415
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发表时间：
2023-02-08
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
肝纤维化是一种以细胞外基质蛋白（ecm）的过度合成和积累为特征的病理过程，主要是由活化的肝星状细胞（hsc）引起的。目前，世界范围内还没有直接有效的抗纤维化药物被批准用于临床。虽然Eph受体酪氨酸激酶EphB2的失调已被报道与肝纤维化的发展有关，但其他Eph家族成员在肝纤维化中的参与仍未得到充分探讨。在本研究中，我们发现活化的hsc中EphB1的表达显著增加，并伴有显着的类化修饰。从机制上讲，这种类化修饰通过阻止EphB1的降解来增强其激酶活性，从而促进造血干细胞的增殖、迁移和活化。我们的研究结果揭示了EphB1通过其类化修饰参与肝纤维化的发展，这为Eph受体信号传导和肝纤维化治疗的潜在靶点提供了新的见解。
Liver fibrosis is a pathological process characterized by the excessive synthesis and accumulation of extracellular matrix proteins (ECMs) contributed mainly by the activated hepatic stellate cells (HSCs). Currently, no direct and effective anti-fibrotic agents have been approved for clinical use worldwide. Although the dysregulation of Eph receptor tyrosine kinase EphB2 has been reported to associate with the development of liver fibrosis, the involvement of other Eph family members in liver fibrosis remains underexplored. In this study, we found that the expression of EphB1 is significantly increased accompanying remarkable neddylation in activated HSCs. Mechanistically, this neddylation enhanced the kinase activity of EphB1 by the prevention of its degradation, thereby promoting the proliferation, migration, and activation of HSCs. Our findings revealed the involvement of EphB1 in the development of liver fibrosis through its neddylation, which provides new insights into the Eph receptor signaling and a potential target for the treatment of liver fibrosis.
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多个EPHB受体酪氨酸激酶在海马中塑造树突状刺。
影响因子：
7.8
作者：
Henkemeyer, Mark;Itkis, Olga S;Ngo, Michelle;Hickmott, Peter W;Ethell, Iryna M
通讯作者：
Ethell, Iryna M
NEDDylation 拮抗增殖细胞核抗原的泛素化并调节聚合酶 eta 的募集以响应氧化 DNA 损伤
影响因子：
21.1
作者：
Guan J;Yu S;Zheng X
通讯作者：
Zheng X
EphB1受体在恶性脑肿瘤中的悖论
影响因子：
5.8
作者：
Wei W;Wang H;Ji S
通讯作者：
Ji S
DOI：
10.1002/hep.27792
发表时间：
2015-09
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Mimche PN;Brady LM;Bray CF;Lee CM;Thapa M;King TP;Quicke K;McDermott CD;Mimche SM;Grakoui A;Morgan ET;Lamb TJ
通讯作者：
Lamb TJ
影响因子：
25.7
作者：
Wilson CL;Murphy LB;Leslie J;Kendrick S;French J;Fox CR;Sheerin NS;Fisher A;Robinson JH;Tiniakos DG;Gray DA;Oakley F;Mann DA
通讯作者：
Mann DA