Overexpression of GLP-1 receptors suppresses proliferation and cytokine release by airway smooth muscle cells of patients with chronic obstructive pulmonary disease via activation of ABCA1

Sun,Yan‑Hong; He,Lan; Yan,Ming‑Yu; Zhao,Rui‑Qian; Li,Bin; Wang,Feng; Yang,Ying; Yu,Hua‑Peng

doi:10.3892/mmr.2017.6618

Overexpression of GLP-1 receptors suppresses proliferation and cytokine release by airway smooth muscle cells of patients with chronic obstructive pulmonary disease via activation of ABCA1

Authors:
- Yan‑Hong Sun
- Lan He
- Ming‑Yu Yan
- Rui‑Qian Zhao
- Bin Li
- Feng Wang
- Ying Yang
- Hua‑Peng Yu
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Affiliations: Department of Respiratory Diseases, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Respiratory Diseases, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China, Department of Respiratory and Critical Medicine, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, Inner Mongolia Autonomous Region 014010, P.R. China, Graduate School, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China, Department of Histology and Embryology, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China, Department of Physiology, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China
Published online on: May 25, 2017 https://doi.org/10.3892/mmr.2017.6618
Pages: 929-936

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Abstract

Glucagon-like peptide-1 (GLP‑1) is an important insulin secretagogue that possesses anti‑inflammatory effects. GLP‑1 receptor (GLP‑1R) agonists have been demonstrated to serve a pivotal role in the treatment of obstructive lung diseases, including chronic obstructive pulmonary disease (COPD). However, the specific function and underlying mechanisms of GLP‑1R in COPD remain uncertain. The aim of the present study was to investigate the action and underlying mechanisms of GLP‑1R in airway smooth muscle (ASM) cells from COPD patients. GLP‑1R expression levels were markedly decreased in ASM cells from COPD patients compared with those from healthy controls. ASM cell proliferation and migration, and the levels of the inflammatory cytokines interleukin (IL)‑1β, IL‑4, tumor necrosis factor (TNF)‑α, and granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) were measured. Transfection of pcDNA3.1‑GLP‑1R had inhibitory effects on ASM cell proliferation and migration, whereas GLP‑1R small interfering (si)RNA reversed these effects. Furthermore, the present study demonstrated that GLP‑1R overexpression markedly suppressed IL‑1β, IL‑4, TNF‑α and GM‑CSF levels. GLP‑1R overexpression upregulated the expression levels of adenosine triphosphate‑binding cassette, subfamily A, member 1 (ABCA1) in ASM cells, and the effects of GLP‑1R on cell proliferation and migration, and inflammatory cytokine expression in ASM cells was abolished by siRNA‑mediated silencing of ABCA1. The results of the present study suggested that GLP‑1R contributes to COPD pathology, potentially via an ABCA1‑mediated pathway.

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