title: SB203580 inhibits epithelial-mesenchymal transition and pulmonary fibrosis in a rat silicosis model.
abstract: To investigate the role of p38 MAPK in silicosis, we explored the effects of SB203580 as a specific inhibitor of p38 MAPK in the silicosis model in rats. Rats were exposed to 50mg/ml silica intratracheally. From the first day after instillation, rats were injected with SB203580 1mg/kg/d. Rats were sacrificed at 7 and 15days after exposure of silica. The results demonstrated SB203580 could prevent the activation of p38. TGF-β1 in bronchoalveolar lavage fluid, the expression of vimentin and α-SMA in the lung tissue was down-regulated and E-cadherin was up-regulated after intervention with SB203580 at 7days and 15days. The percentage of the cells staining with SP-C and vimentin doubly was lower in SB203580 treated group than in silica group at 7days and 15days. SB203580 also inhibited the increase of ZEB-1, ZEB-2 and Twist at 7days. Histopathologic examination showed the decrease in the number of nodules and the blue areas of collagen fibers in the lung after SB203580 treatment. The content of hydroxyproline and the expression of collagen I and III decreased in SB203580 treated group than in silica group. These results suggested that p38 MAPK/ZEB-1 (ZEB-2, Twist) pathway was involved at 7days after silica instillation and p38 MAPK was pivotal for EMT in silicosis fibrosis in rats.
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xiaoli
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: An
authors.initials: A
authors.lastname: Guoliang
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhonghui
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Di
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Ximeng
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Niu
authors.initials: N
authors.lastname: Piye
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: tian_lin@163.com.
authors.forename: Tian
authors.initials: T
authors.lastname: Lin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000188:drug therapy*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D011725:Pyridines; D012822:Silicon Dioxide; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: EMT; Pulmonary fibrosis; SB203580; Silica; p38 MAPK