# Adipose Tissue-Derived Exosome and miR-142a-3p Alleviate Acute Lung Injury by Inhibiting HMGB1-Driven Autophagy

## TL;DR

Adipose tissue exosomes and miR-142a-3p reduce lung injury by blocking harmful autophagy, offering potential new treatments.

## Contribution

Identifies miR-142a-3p and adipose-derived exosomes as novel therapeutic agents for acute lung injury.

## Key findings

- Adipose-derived exosomes from lean or obese mice equally reduce LPS-induced lung injury by inhibiting autophagy.
- miR-142a-3p specifically targets HMGB1 mRNA to suppress autophagy and alleviate lung damage.
- Both exosomes and miR-142a-3p show therapeutic potential for treating acute lung injury.

## Abstract

What are the main findings?
Adipose-derived exosomes and miR-142a-3p attenuate LPS-induced ALI by suppressing HMGB1-driven autophagy in ALI.Exosomes from lean or DIO mouse exert comparable anti-autophagy effects and protect against LPS-induced ALI.

Adipose-derived exosomes and miR-142a-3p attenuate LPS-induced ALI by suppressing HMGB1-driven autophagy in ALI.

Exosomes from lean or DIO mouse exert comparable anti-autophagy effects and protect against LPS-induced ALI.

What are the implications of the main findings?
Inhibition of pulmonary autophagy by regulating HMGB1 may contribute to a therapeutic effect.Exosomes and miRNAs targeting HMGB1 may hold potential as novel treatment strategies for ALI.

Inhibition of pulmonary autophagy by regulating HMGB1 may contribute to a therapeutic effect.

Exosomes and miRNAs targeting HMGB1 may hold potential as novel treatment strategies for ALI.

Acute lung injury (ALI) is a clinically severe respiratory disorder, of which autophagy is the crucial mechanism. Exosomes have the potential to treat ALI, but the role of adipose-derived exosomes (ADEs) in the autophagy of ALI remains unclear. Using an LPS-induced ALI model, the effects of ADE isolated from a lean or diet-induced-obese (DIO) mouse and ADE-carried miRNAs were investigated. After administration of ADEs, the levels of autophagy-related molecules were determined by qRT-PCR, Western blotting, and immunohistochemical staining. Then, a miRNA targeting HMGB1 was screened by bioinformatic analysis and a dual-luciferase reporter assay, and its effect on the HMGB1-driven autophagy in an ALI mouse was investigated as ADEs. The data showed that LPS caused lung injury and activated HMGB1-driven autophagy. The ADEs from a lean mouse or DIO mouse significantly alleviated histopathological lesions, and they inhibited HMGB1-driven autophagy by down-regulating LC3, Beclin-1, and Atg5; the effects of ADEs were not significantly different between a lean and DIO mouse. Of the miRNAs carried by ADE, moreover, miR-142a-3p could specifically bind to HMGB1 mRNA, and up-regulation of pulmonary miR-142a-3p suppressed HMGB1-driven autophagy and relieved lung injuries. Our results indicated that miR-142a-3p and ADEs mitigate LPS-induced ALI by inhibiting HMGB1-driven autophagy, providing new insights on the prevention and treatment of ALI.