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ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-κB signaling pathway in primary biliary cholangitis

Ma, Di, Liu, Xiaoxiao, Li, Jinyu, Wu, Hanxin, Ma, Jiaxuan, Tai, Wenlin·2024·Digestive and Liver Disease

Abstract

Background & aims Primary biliary cholangitis (PBC), a typical autoimmune liver disease, is characterized by an increased infiltration of immune cells. However, the specific molecular mechanisms regulating immune cell migration in PBC are unknown. Engulfment and cell motility 1 (ELMO1) plays an important function in cellular dynamics. In view of this, the aim of this study was to explore the expression of ELMO1 in PBC, its effects on the proliferation, migration, and secretion of inflammatory factors by the mainly regulated immune cells and the specific molecular mechanisms behind it. Methods To determine the expression of ELMO1 in PBC and its major regulatory immune cells in PBC. The migratory and proliferative capacities of ELMO1-deficient macrophages were measured, and their pro-inflammatory cytokine secretion was also detected and explored mechanistically. Results ELMO1 expression was up-regulated in the PBC patients and positively correlated with alkaline phosphatase (ALP). ELMO1 mainly regulated macrophages in the liver of PBC patients. Knockdown of ELMO1 did not affect macrophage proliferation, however,knockdown of ELMO1 significantly inhibited macrophage migration,downstream RAC1 activity was diminished, and reduced F-actin synthesis. Knockdown of ELMO1 reduced macrophage inflammatory factor secretion and NF-κB signaling pathway activity was decreased. Conclusions ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-κB signaling pathway in…

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Metadata

Authors
Ma, D., Liu, X., Li, J., Wu, H., Ma, J., & Tai, W.
Venue
Digestive and Liver Disease
Publisher
Elsevier BV
Published
2024-11
Volume
56
Issue
11
Pages
1897-1905
ISSN
1590-8658
Cited by
7
References
3
Language
en
Funders
  • Kunming Medical University
  • National Natural Science Foundation of China (82060385, 82060385,81760383, 81760383)

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Ma, D., Liu, X., Li, J., Wu, H., Ma, J., & Tai, W. (2024). ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-κB signaling pathway in primary biliary cholangitis. Digestive and Liver Disease. https://doi.org/10.1016/j.dld.2024.05.012