biostudies-literatureUnknown9(6)Liu J<h4>Background</h4>Extracellular matrix proliferation is an issue which leads to lung tissue damage in diabetes mellitus. Glucagon-like peptide-1 (GLP-1) analogues can improve the proliferation of extracellular matrix in diabetic pulmonary disease. In this study, we investigated the effect of GLP-1 on pulmonary fibrosis through the AMPK/microRNA-27a (miR-27a) pathway.<h4>Methods</h4>Human embryonic lung fibroblast (MRC-5) cells were cultured with a high-glucose medium, and were treated with miR-27a inhibitor, GLP-1 analogues, and AMPK inhibitor. Cell Counting Kit-8 (CCK-8) detected the proliferation of MRC-5 cells. The fibrosis-related genes were analyzed, including Col-IV, fibronectin, NF-κB p65, α-SMA, and TGF-β1. Bioinformatics and dual-luciferase reporter assays were used to identify the targets for miR-27a.<h4>Results</h4>Compared with the control group, the expression of miR-27a in the hyperglycemic group was significantly up-regulated (P<0.01) and the expression of peroxisome proliferator-activated receptor γ (PPARγ) significantly down-regulated (P<0.01). The expression of Col-IV, fibronectin, NF-κB p65, α-SMA and TGF-β1 increased significantly (P<0.01). The expression level of apoptosis factor caspase-3 decreased significantly (P<0.01). MiR-27a inhibitor could reverse the expression of these proteins. The effect of GLP-1 on miR-27a was time- and concentration-dependent. After pretreating MRC-5 cells via GLP-1, with or without compound C (AMPK inhibitor), the expression of miR-27a in the GLP-1 treated group was significantly lower than that in Vehicle group. The expression of miR-27a was increased after inhibition of the AMPK pathway. A predictive TargetScan algorithm showed that the PPARγ gene was a potential target of miR-27a. MiR-27a was also shown to target 3'-UTR of PPARγ.<h4>Conclusions</h4>MiR-27a plays an important regulatory role in diabetic pulmonary fibrosis. GLP-1 could down-regulate the expression level of miR-27a by activating AMPK. Furthermore, the target gene PPARγ was up-regulated, consequently improving extracellular matrix proliferation in MRC-5 cells.Annals of translational medicine492https://www.ebi.ac.uk/biostudies/studies/S-EPMC8039657biostudies-literatureGlucagon-like peptide-1 (GLP-1) improved diabetic lung fibrosis via AMPK and microRNA-27a (miR-27a).PMC8039657Li XLiu JZheng XZhang XLu SZhao WfalseGlucagon-like peptide-1 (GLP-1) improved diabetic lung fibrosis via AMPK and microRNA-27a (miR-27a).<h4>Background</h4>Extracellular matrix proliferation is an issue which leads to lung tissue damage in diabetes mellitus. Glucagon-like peptide-1 (GLP-1) analogues can improve the proliferation of extracellular matrix in diabetic pulmonary disease. In this study, we investigated the effect of GLP-1 on pulmonary fibrosis through the AMPK/microRNA-27a (miR-27a) pathway.<h4>Methods</h4>Human embryonic lung fibroblast (MRC-5) cells were cultured with a high-glucose medium, and were treated with miR-27a inhibitor, GLP-1 analogues, and AMPK inhibitor. Cell Counting Kit-8 (CCK-8) detected the proliferation of MRC-5 cells. The fibrosis-related genes were analyzed, including Col-IV, fibronectin, NF-κB p65, α-SMA, and TGF-β1. Bioinformatics and dual-luciferase reporter assays were used to identify the targets for miR-27a.<h4>Results</h4>Compared with the control group, the expression of miR-27a in the hyperglycemic group was significantly up-regulated (P<0.01) and the expression of peroxisome proliferator-activated receptor γ (PPARγ) significantly down-regulated (P<0.01). The expression of Col-IV, fibronectin, NF-κB p65, α-SMA and TGF-β1 increased significantly (P<0.01). The expression level of apoptosis factor caspase-3 decreased significantly (P<0.01). MiR-27a inhibitor could reverse the expression of these proteins. The effect of GLP-1 on miR-27a was time- and concentration-dependent. After pretreating MRC-5 cells via GLP-1, with or without compound C (AMPK inhibitor), the expression of miR-27a in the GLP-1 treated group was significantly lower than that in Vehicle group. The expression of miR-27a was increased after inhibition of the AMPK pathway. A predictive TargetScan algorithm showed that the PPARγ gene was a potential target of miR-27a. MiR-27a was also shown to target 3'-UTR of PPARγ.<h4>Conclusions</h4>MiR-27a plays an important regulatory role in diabetic pulmonary fibrosis. GLP-1 could down-regulate the expression level of miR-27a by activating AMPK. Furthermore, the target gene PPARγ was up-regulated, consequently improving extracellular matrix proliferation in MRC-5 cells.2021-01-01T00:00:00Z2021 Mar2025-04-04T21:24:44.002Z2025-04-04T21:24:44.002ZS-EPMC80396573385088910.21037/atm-21-869