miR-141-3p attenuates inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway.
Immunol Res
; 2024 Jun 12.
Article
en En
| MEDLINE
| ID: mdl-38865000
ABSTRACT
The present research aimed to investigate the effects and mechanisms of microRNA (miR)-141-3p on pulmonary fibrosis of acute respiratory distress syndrome (ARDS). A rat ARDS model was established by the intratracheal drip of 10 mg/kg lipopolysaccharide (LPS). miR-141-3p and Kelch-like ECH-associated protein 1 (Keap1) expression was detected using RT-qPCR assay. Inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissues were measured with enzyme-linked immunosorbent assay (ELISA). Lung fibrosis was evaluated using Masson's trichrome staining and hydroxyproline assay kits. Tissue oxidative stress marker levels were assessed by a commercial kit. Protein variations in the EMT pathway and Keap1/nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway were investigated by Western blot analysis. Targeting relationship verified by dual-luciferase reporter assay. The expression of miR-141-3p was significantly upregulated in LPS-induced ARDS rats, while Keap1 was downregulated. Overexpression of miR-141-3p decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, superoxide dismutase (SOD), and glutathione (GSH) while elevating malondialdehyde (MDA) expression in LPS-induced ARDS rats. Elevation of miR-141-3p reduced fibrosis scores, enhanced E-cadherin protein expression, and decreased vimentin and α-SMA protein expression in LPS-induced ARDS rats. This elevation of miR-141-3p also upregulated Nrf2, heme oxygenase-1 (HO-1), and NAD(P)Hquinone oxido-reductase-1 (NQO1) proteins levels. Moreover, Keap1 overexpression reversed the inhibitory effects of miR-141-3p on LPS-triggered inflammation, oxidative stress, and fibrosis. miR-141-3p may attenuate inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway. Our study provides new ideas for the treatment of ARDS.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Immunol Res
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos