The downregulation of miR-129-5p relieves the inflammatory response in acute respiratory distress syndrome by regulating PPARγ-mediated autophagy.

Abstract

Background:

The peroxisome proliferator-activated receptor γ (PPARγ) promotes autophagy and regulates the inflammatory response. However, the effects of the PPARγ on inflammation in acute respiratory distress syndrome (ARDS) are unclear. This study sought to explore the mechanism by which the downregulation of microRNA-129-5p (miR-129-5p) attenuates the inflammatory response in ARDS patients by regulating PPARγ-mediated autophagy.

Methods:

Lipopolysaccharide (LPS) was used to establish an acute lung injury (ALI) mice model to simulate ARDS. GW9662 and pioglitazone were applied to inhibit and activate the PPARγ, respectively. Enzyme-linked immunoassays were used to detect inflammatory cytokines. The expressions of miR-129-5p, the PPARγ, and the autophagy-marker protein were detected by quantitative polymerase chain reaction (qPCR) or Western blot. Dual-luciferase reporter assays were used to verify the targeting relationship between miR-129-5p and PPARγ messenger RNA (mRNA). Human lung epithelial cells BEAS-2B transfected with the miR-129-5p inhibitor and/or the short interfering RNA PPARγ (si-PPARγ) were applied to explore the mechanism.

Results:

The results showed that pioglitazone promoted autophagy and relieved lung injury caused by LPS, while GW9662 exacerbated lung injury. MiR-129-5p directly targeted the PPARγ. Inhibiting the expression of miR-129-5p increased the level of the PPARγ, induced autophagy, and inhibited apoptosis and the inflammatory response. Conversely, silencing the PPARγ had the opposite effects, and blocked the protective effects of the miR-129-5p inhibitor.

Conclusions:

The inhibition of miR-129-5p may induce autophagy and inhibit the inflammatory response by promoting the expression of the PPARγ, thereby relieving ARDS.

• Authors: Duan Zhu, Mi Zhou, Kang Wang, Xueting Hu, Liang Gong, Hu Luo, Xiangdong Zhou, Jianlin Hu
• Journal: Annals of translational medicine (Ann Transl Med) Vol. 10 Issue 6 Pg. 345 (Mar 2022) ISSN: 2305-5839 [Print] China
• PMID: 35433953 (Publication Type: Journal Article)
• Copyright: 2022 Annals of Translational Medicine. All rights reserved.