Thal protects against paraquat‐induced lung injury through a microRNA‐141/HDAC6/IκBα‐NF‐κB axis in rat and cell models. Issue 2 (14th October 2020)

• Record Type: Journal Article
• Authors: Zheng, Fenshuang; Zhu, Junbo; Zhang, Wei; Fu, Yangshan; Lin, Zhaoheng
• Is Part Of: Basic & clinical pharmacology & toxicology. Volume 128:Issue 2(2021)
• Page Start: 334
• Page End: 347
• Publication Date: 2020-10-14
• Subjects: gene expression -- lung injury -- Paraquat -- risk assessment -- thalidomide -- viability -- Wistar rat; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology, Clinical -- Periodicals; Computer network resources; Electronic journals; 615.1
• DOI: 10.1111/bcpt.13505
• Languages: English
• ISSNs: 1742-7835

Abstract

Abstract: The protective functions of thalidomide in paraquat (PQ)‐induced injury have been reported. But the mechanisms remain largely unknown. In this research, a PQ‐treated rat model was established and further treated with thalidomide. Oedema and pathological changes, oxidative stress, inflammation, fibrosis and cell apoptosis in rat lungs were detected. A PQ‐treated RLE‐6TN cell model was constructed, and the viability and apoptosis rate of cells were measured. Differentially expressed microRNAs (miRNAs) after thalidomide administration were screened out. Binding relationship between miR‐141 and histone deacetylase 6 (HDAC6) was validated. Altered expression of miR‐141 and HDAC6 was introduced to identify their involvements in thalidomide‐mediated events. Consequently, thalidomide administration alone exerted no damage to rat lungs; in addition it reduced PQ‐induced oedema. The oxidative stress, inflammation and cell apoptosis in rat lungs were reduced by thalidomide. In RLE‐6TN cells, thalidomide increased cell viability and decreased apoptosis. miR‐141 was responsible for thalidomide‐mediated protective events by targeting HDAC6. Overexpression of HDAC6 blocked the protection of thalidomide against PQ‐induced injury via activating the IkBα‐NF‐κB signalling pathway. Collectively, this study evidenced that thalidomide protects lung tissues from PQ‐induced injury through a miR‐141/HDAC6/IkBα‐NF‐κB axis.