Ribosomal Protein S3 Gene Silencing Protects Against Cigarette Smoke-Induced Acute Lung Injury
Overview
Affiliations
Chronic obstructive pulmonary disease (COPD) is estimated to be the third leading cause of death by 2030. Transcription factor NF-κB may play a critical role in COPD pathogenesis. Ribosomal protein S3 (RPS3), a 40S ribosomal protein essential for executing protein translation, has recently been found to interact with the NF-κB p65 subunit and promote p65 DNA-binding activity. We sought to study whether RPS3 gene silencing could protect against cigarette-smoke (CS)-induced acute lung injury in a mouse model. Effects of an intratracheal RPS3 siRNA in CS-induced lung injury were determined by measuring bronchoalveolar lavage (BAL) fluid cell counts, levels of inflammatory and oxidative damage markers, and NF-κB translocation. Lung RPS3 level was found to be upregulated for the first time with CS exposure, and RPS3 siRNA blocked CS-induced neutrophil counts in BAL fluid. RPS3 siRNA suppressed CS-induced lung inflammatory mediator and oxidative damage marker levels, as well as nuclear p65 accumulation and transcriptional activation. RPS3 siRNA was able to disrupt CS extract (CSE)-induced NF-κB activation in an NF-κB reporter gene assay. We report for the first time that RPS3 gene silencing ameliorated CS-induced acute lung injury, probably via interruption of the NF-κB activity, postulating that RPS3 is a novel therapeutic target for COPD.
Hussain N, Ikram N, Khan K, Hussain L, Alqahtani A, Alqahtani T Heliyon. 2023; 9(11):e22055.
PMID: 38045213 PMC: 10692792. DOI: 10.1016/j.heliyon.2023.e22055.
De Rubis G, Paudel K, Corrie L, Mehndiratta S, Patel V, Kumbhar P Naunyn Schmiedebergs Arch Pharmacol. 2023; 397(5):2793-2833.
PMID: 37991539 DOI: 10.1007/s00210-023-02830-w.
Zhang C, Bai H, Zhang L, Zhang Y, Chen X, Shi R Sci Rep. 2022; 12(1):11667.
PMID: 35804020 PMC: 9270349. DOI: 10.1038/s41598-022-15859-3.
Inhaled siRNA Formulations for Respiratory Diseases: From Basic Research to Clinical Application.
Fan Y, Yang Z Pharmaceutics. 2022; 14(6).
PMID: 35745766 PMC: 9227582. DOI: 10.3390/pharmaceutics14061193.
Li J, Xue L, Wu Y, Yang Q, Liu D, Yu C J Cell Mol Med. 2021; 25(14):6550-6557.
PMID: 34114724 PMC: 8278113. DOI: 10.1111/jcmm.16653.