Adiponectin attenuates lung fibroblasts activation and pulmonary fibrosis induced by paraquat

• Published in: PloS one 2015-05, Vol.10 (5), p.e0125169
• Main Authors: Yao, Rong, Cao, Yu, He, Ya-rong, Lau, Wayne Bond, Zeng, Zhi, Liang, Zong-an
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Activation; Adiponectin; Adiponectin - therapeutic use; Animals; Annexin V; Apoptosis; Apoptosis - drug effects; Blood; Blood levels; Cell Line; Cell Survival; Cellular proteins; Cholecystokinin; Collagen (type III); Collagen Type III - biosynthesis; Collagen Type III - genetics; Complications; Connective tissue growth factor; Connective Tissue Growth Factor - metabolism; Development and progression; Drug dosages; Emergency medical care; Enzyme-linked immunosorbent assay; Fibroblasts; Fibroblasts - pathology; Fibrosis; Fluorescein; Fluorescence; Gelatinase B; Gene expression; Genetic aspects; Growth factors; Health aspects; Hospitals; Humans; Life sciences; Lung - pathology; Lung diseases; Male; Matrix Metalloproteinase 9 - blood; Medical research; Medicine; Mice; Mice, Inbred BALB C; Paraquat; Paraquat - poisoning; Polymerase chain reaction; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - physiopathology; Random Allocation; Receptors, Adiponectin - biosynthesis; Receptors, Adiponectin - genetics; Ribonucleic acid; RNA; RNA Interference; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Small Interfering; Rodents; siRNA; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - blood; Toxicology; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125169

Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which demands for more effective therapies. Accumulating evidence suggests adiponectin (APN) may be a promising therapy against fibrotic diseases. In the current study, we determine whether the exogenous globular APN isoform protects against pulmonary fibrosis in PQ-treated mice and human lung fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We compared pulmonary histopathological changes among different groups on the basis of fibrosis scores, TGF-β1, CTGF and α-SMA pulmonary content via Western blot and real-time quantitative fluorescence-PCR (RT-PCR). Blood levels of MMP-9 and TIMP-1 were determined by ELISA. Human lung fibroblasts WI-38 were divided into control group, PQ group, APN group, and APN receptor (AdipoR) 1 small-interfering RNA (siRNA) group. Fibroblasts were collected 24, 48, and 72 hours after PQ exposure for assay. Cell viability and apoptosis were determined via Kit-8 (CCK-8) and fluorescein Annexin V-FITC/PI double labeling. The protein and mRNA expression level of collagen type III, AdipoR1, and AdipoR2 were measured by Western blot and RT-PCR. APN treatment significantly decreased the lung fibrosis scores, protein and mRNA expression of pulmonary TGF-β1, CTGF and α-SMA content, and blood MMP-9 and TIMP-1 in a dose-dependent manner (p