Open AccessEffects of Akt Inhibition on The Regulatory and Proteomic Profiles of Alveolar Macrophages Enriched from Lung Lavages of Pulmonary Fibrosis Patients
Author(s) -
Meiling Gou,
Mengqiao Wang
Publication year - 2022
Publication title -
frontiers in medical case reports
Language(s) - English
Resource type - Journals
ISSN - 2582-8142
DOI - 10.47746/fmcr.2022.3101
Subject(s) - pulmonary fibrosis , pi3k/akt/mtor pathway , autophagy , protein kinase b , transcriptome , fibrosis , alveolar macrophage , signal transduction , cytokine , lung , cancer research , microbiology and biotechnology , medicine , biology , apoptosis , immunology , gene , gene expression , macrophage , pathology , genetics , in vitro
Objective: pulmonary fibrosis caused by pneumoconiosis is an irreversible disease, and there is a lack of treatment at present. The alveolar macrophages of patients were treated with Akt inhibitor MK-2206 to explore the changes of transcriptome expression and enrichment pathway, so as to provide reference targets for clinical medication. Materials: Purification and lab assays of alveolar macrophages from whole lung lavages of pulmonary fibrosis patients. Methods: RNA-seq was used to analyze alveolar macrophages before and after MK-2206 treatment to obtain subgroups of differentially expressed genes, which were further subjected to the analysis of the function and pathway enrichment. Key targets of main pathways were obtained through protein-protein interaction network analysis, providing information for the underlying connected regulatory mechanisms. Results: 143 up-regulated and 110 down-regulated genes were obtained by differential gene analysis. The up-regulated genes were mainly enriched in longevity regulation pathway, autophagy pathway and mTOR pathway, and the down-regulated genes were mainly enriched in inflammatory response and cytokine- cytokine interaction pathway. MK-2206 regulated alveolar macrophages in pulmonary fibrosis through the above two aspects. Conclusion: MK2206, as a specific inhibitor of the Akt, could potentially affect its downstream pathway to regulate the process of autophagy and apoptosis. In addition, it also reduces the release and interaction of cytokines, and jointly regulate the process of pulmonary fibrosis. Clinically, MK-2206 can combine and cooperate with other targets to provide reference for drug treatment.