1. Adipose-Derived exosome from Diet-Induced-Obese mouse attenuates LPS-Induced acute lung injury by inhibiting inflammation and Apoptosis: In vivo and in silico insight.
- Author
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Wang F, Zeng L, Chi Y, Yao S, Zheng Z, Peng S, Wang X, and Chen K
- Subjects
- Animals, Mice, Male, Inflammation, Disease Models, Animal, Lung pathology, Lung immunology, Humans, Mice, Obese, Diet, High-Fat adverse effects, Acute Lung Injury immunology, Acute Lung Injury chemically induced, Exosomes metabolism, Apoptosis, MicroRNAs metabolism, MicroRNAs genetics, Adipose Tissue metabolism, Obesity, Lipopolysaccharides, Mice, Inbred C57BL, Cytokines metabolism
- Abstract
Background: Acute lung injury (ALI) is a severe clinical condition in the intensive care units, and obesity is a high risk of ALI. Paradoxically, obese ALI patients had better prognosis than non-obese patients, and the mechanism remains largely unknown., Methods: Mouse models of ALI and diet-induced-obesity (DIO) were used to investigate the effect of exosomes derived from adipose tissue. The adipose-derived exosomes (ADEs) were isolated by ultracentrifugation, and the role of exosomal miRNAs in the ALI was studied., Results: Compared with ADEs of control mice (C-Exo), ADEs of DIO mice (D-Exo) increased survival rate and mitigated pulmonary lesions of ALI mice. GO and KEGG analyses showed that the target genes of 40 differentially expressed miRNAs between D-Exo and C-Exo were mainly involved with inflammation, apoptosis and cell cycle. Furthermore, the D-Exo treatment significantly decreased Ly6G
+ cell infiltration, down-regulated levels of pro-inflammatory cytokines (IL-6, IL-12, TNF-α, MCP-1) and chemokines (IL-8 and MIP-2), reduced pulmonary apoptosis and arrest at G0 G1 phase (P < 0.01). And the protective effects of D-Exo were better than those of C-Exo (P < 0.05). Compared with the C-Exo mice, the levels of miR-16-5p and miR-335-3p in the D-Exo mice were significantly up-regulated (P < 0.05), and the expressions of IKBKB and TNFSF10, respective target of miR-16-5p and miR-335-3p by bioinformatic analysis, were significantly down-regulated in the D-Exo mice (P < 0.05)., Conclusions: Exosomes derived from adipose tissue of DIO mice are potent to attenuate LPS-induced ALI, which could be contributed by exosome-carried miRNAs. Our data shed light on the interaction between obesity and ALI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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