2. Academic Validation
  3. MiR-124-3p targeting PDE4B attenuates LPS-induced ALI through the TLR4/NF-κB signaling pathway

MiR-124-3p targeting PDE4B attenuates LPS-induced ALI through the TLR4/NF-κB signaling pathway

  • Int Immunopharmacol. 2022 Apr:105:108540. doi: 10.1016/j.intimp.2022.108540.
Qiao Zhou 1,  Ding-Xiu He 1,  Yi-Ling Deng 2,  Chun-Li Wang 2,  Lan-Lan Zhang 3,  Fa-Ming Jiang 1,  Laurent Irakoze 4,  Zong-An Liang 5
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
  • 2 Pathology Laboratory of Sichuan University, Chengdu, Sichuan, China.
  • 3 Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China. Electronic address: [email protected].
  • 4 Internal Medicine Department, Roi Khaled Hospital of Burundi University, Bujumbura, Burundi.
  • 5 Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China. Electronic address: [email protected].
PMID: 35063752 DOI: 10.1016/j.intimp.2022.108540
Abstract

Background: A large number of studies have found that MicroRNAs (miRNAs) and phosphodiesterase 4 (PDE4) are crucial regulators of inflammatory responses in acute lung injury (ALI).

Objective: This study will explore the protective effect of miR-124-3p on ALI and its related mechanism.

Methods: The ALI mouse model was established by intratracheal administration of lipopolysaccharide (LPS) and evaluated by haematoxylin and eosin (HE) staining, lung injury score, inflammation factors, polymorphonuclear leukocyte (PMN) count, total protein and lung wet weight/dry weight (W/D) ratio. MiR-124-3p was overexpressed in vivo by intratracheal administration of miR-agomir, and PDE4B was expressed at low level in vivo by intratracheal administration of a PDE4B inhibitor. The mRNA expression level was detected by qRT-PCR, and the protein expression level was detected by Western blot. The relationship between miR-124-3p and PDE4B was detected by dual-luciferase activity assay.

Results: We found that miR-124-3p was downregulated in LPS-induced ALI. Overexpression of miR-124-3p alleviated lung injury by inhibiting the Toll-like Receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, we confirmed that miR-124-3p suppressed the TLR4/NF-κB signaling pathway by directly targeting PDE4B.

Conclusion: miR-124-3p targeting PDE4B had a protective effect on LPS-induced ALI by inhibiting the TLR4/NF-κB signaling pathway.

Keywords

ALI; LPS; MiR-124-3p; PDE4B; TLR4/NF-κB.

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