Neddylation of EphB1 Regulates Its Activity and Associates with Liver Fibrosis

Author:

Li Rongxin1,Zhang Dan1,Han Yueqing1,Chen Ke1,Guo Weiran1,Chen Yijun1ORCID,Wang Shuzhen1ORCID

Affiliation:

1. School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China

Abstract

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.

Funder

National Key R&D Program of China

National Science Foundation of China

Double First-Class University Plan

State Key Laboratory of Natural Medicines, China Pharmaceutical University

Priority Academic Program Development of Jiangsu Higher Education Institutions

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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