1. CX3CR1 regulates angiogenesis and activation of pro-angiogenic factors and triggers macrophage accumulation in experimental hepatopulmonary syndrome model.
- Author
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Liu H, Gu H, Gu L, Liao J, Yang X, Wu C, Ran X, Feng X, Zuo S, and Li H
- Subjects
- Animals, Disease Models, Animal, Male, Mice, Mice, Inbred C57BL, CX3C Chemokine Receptor 1 physiology, Hepatopulmonary Syndrome etiology, Macrophages physiology, Neovascularization, Pathologic etiology
- Abstract
Objective: Prevalence of hepatopulmonary syndrome (HPS) ranges from 4% to 47% in patients with cirrhosis. This study aimed to explore possible relationship between CX3CR1 and angiogenesis or macrophage accumulation in pathological process of HPS., Material and Methods: Wide-type C57Bl/6 mice were divided into WT-sham, WT-common bile duct ligation (WT-CBDL), WT-CBDL plus antibody (WT-CBDL+Ab) and WT-CBDL plus Bevacizumab. The CX3CR1
GFP/GFP mice were grouping into CX3CR1 GFP/GFP-sham, CX3CR1 GFP/GFP-CBDL and CX3CR1 GFP/GFP-CBDL+Bevacizumab group. Intrapulmonary expression of Akt, pAkt, ERK, pERK, iNOS, VEGF, PDGF was measured using biological technology. Hematoxylin-eosin (H&E) staining and immunohistochemical analysis were used to evaluate changes of pulmonary tissues including pathological abnormality, angiogenesis and macrophage accumulation., Results: Blockade CX3CR1 pathway inhibited angiogenesis, macrophage accumulation and pathological changes of lung tissues. Blockade of CX3CR1 pathway reduced pAkt, pERK, iNOS, PDGF and VEGF activation. CX3CR1 contributed to the process of angiogenesis and activate the pro-angiogenic factors. CX3CR1 deficiency obviously reduced the macrophage accumulation. Inhibition of VEGF by Bevacizumab improved intrapulmonary angiogenesis and pathological changes of lung tissues. Inhibition of VEGF by Bevacizumab retarded the production of pAKt, PDGF, and iNOS. Inhibition of VEGF by Bevacizumab reduced CX3CL1 production., Conclusion: CX3CR1 could regulate the angiogenesis and activation of pro-angiogenic factors, including pAKT, pERK, iNOS, VEGF and PDGF in the process of hepato-pulmonary syndrome. Moreover, CX3CR1 could also contribute to the macrophage accumulation., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)- Published
- 2021
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