title: Bone marrow mesenchymal stem cells attenuate silica-induced pulmonary fibrosis via paracrine mechanisms.
abstract: The purpose of this study was to investigate the anti-fibrotic effect and possible mechanism of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung injury and fibrosis in vivo and in vitro. In vivo, rats were exposed to 50mg/ml silica intratracheally. The rats were sacrificed on day 15 or day 30 after intravenous injection of BMSCs. Histopathological examination demonstrated that BMSCs decreased the blue areas of collagen fibers and the number of nodules. Alveolar epithelium was damaged by silica, but it was restored by BMSCs. In vitro, BMSCs co-cultured with RLE-6TN cells in 6-Transwell plates were evaluated to determine the possible mechanism. The results demonstrated that BMSCs downregulated the expression of collagen I and III. BMSCs reversed morphological abnormalities and reduced the proliferation of RLE-6TN cells. These data showed that BMSCs did not give rise to alveolar epithelial cells directly, while the levels of hepatocyte growth factor, keratinocyte growth factor and bone morphogenetic protein -7 increased and expression of tumor necrosis factor-α and transforming growth factor-β1 decreased in the 6TN+Silica+BMSCs group compared with the 6TN+Silica group. Our results revealed that BMSCs exerted anti-fibrotic effects on silica-induced pulmonary fibrosis, which might be associated with paracrine mechanisms rather than differentiation.
authors.affiliation: School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: An
authors.affiliation: Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liang
authors.affiliation: School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Ximeng
authors.initials: X
authors.lastname: Lian
authors.affiliation: School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Piye
authors.initials: P
authors.lastname: Niu
authors.affiliation: School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Guo
authors.affiliation: 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: Lin
authors.initials: L
authors.lastname: Tian
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005260:Female; D055370:Lung Injury / Q000139:chemically induced / Q000628:therapy; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D011650:Pulmonary Alveoli / Q000166:cytology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000628:therapy*; D000067996:RAW 264.7 Cells; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000737:chemistry* / Q000633:toxicity*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide; D003094:Collagen
keywords: Bone marrow mesenchymal stem cells; Differentiation; Paracrine; Pulmonary fibrosis; Silicosis