title: Glucagon like peptide-1 attenuates bleomycin-induced pulmonary fibrosis, involving the inactivation of NF-κB in mice.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality and poor prognosis. Previous studies confirmed that NF-κB plays a critical role in the pathogenesis of pulmonary fibrosis and glucagon like peptide-1 (GLP-1) has a property of anti-inflammation by inactivation of NF-κB. Furthermore, the GLP-1 receptor was detected in the lung tissues. Our aim was to investigate the potential value and mechanisms of GLP-1 on BLM-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with or without GLP-1 administration. 28 days after BLM infusion, the number of total cells, macrophages, neutrophils, lymphocytes, and the content of TGF-β1 in BALF were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT) staining were performed. The Ashcroft score and hydroxyproline content were analyzed. RT-qPCR and western blot were used to evaluate the expression of α-SMA and VCAM-1. The phosphorylation of NF-κB p65 was also assessed by western blot. DNA binding of NF-κB p65 was measured through Trans(AM) p65 transcription factor ELISA kit. GLP-1 reduced inflammatory cell infiltration and the content of TGF-β1 in BLAF in mice with BLM injection. The Ashcroft score and hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM-induced overexpression of α-SMA and VCAM-1 were blocked by GLP-1 treatment in mice. GLP-1 also reduced the ratio of phosphor-NF-κB p65/total-NF-κB p65 and NF-κB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice. Our data found that BLM-induced lung inflammation and pulmonary fibrosis were significantly alleviated by GLP-1 treatment in mice, possibly through inactivation of NF-κB.
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Si
authors.initials: S
authors.lastname: Gou
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Xi-chen
authors.initials: XC
authors.lastname: Wang
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China; Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China. Electronic address: zhonghua_chen24@sohu.com.
authors.forename: Zhong-hua
authors.initials: ZH
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000199:Actins; D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D016328:NF-kappa B; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; C544013:alpha-smooth muscle actin, mouse; D001761:Bleomycin; D052216:Glucagon-Like Peptide 1; D003094:Collagen; D004247:DNA; D006909:Hydroxyproline
keywords: Glucagon like peptide-1; Inflammation; Nuclear factor-kappa B; Pulmonary fibrosis; Transforming growth factor-beta1