title: Inhibition of bleomycin-induced pulmonary fibrosis by bone marrow-derived mesenchymal stem cells might be mediated by decreasing MMP9, TIMP-1, INF-γ and TGF-β.
abstract: The study was aimed to investigate the mechanism and administration timing of bone marrow-derived mesenchymal stem cells (BMSCs) in bleomycin (BLM)-induced pulmonary fibrosis mice. Thirty-six mice were divided into six groups: control group (saline), model group (intratracheal administration of BLM), day 1, day 3 and day 6 BMSCs treatment groups and hormone group (hydrocortisone after BLM treatment). BMSCs treatment groups received BMSCs at day 1, 3 or 6 following BLM treatment, respectively. Haematoxylin and eosin and Masson staining were conducted to measure lung injury and fibrosis, respectively. Matrix metalloproteinase (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP-1), γ-interferon (INF-γ) and transforming growth factor β1 (TGF-β) were detected in both lung tissue and serum. Histologically, the model group had pronounced lung injury, increased inflammatory cells and collagenous fibres and up-regulated MMP9, TIMP-1, INF-γ and TGF-β compared with control group. The histological appearance of lung inflammation and fibrosis and elevation of these parameters were inhibited in BMSCs treatment groups, among which, day 3 and day 6 treatment groups had less inflammatory cells and collagenous fibres than day 1 treatment group. BMSCs might suppress lung fibrosis and inflammation through down-regulating MMP9, TIMP-1, INF-γ and TGF-β. Delayed BMSCs treatment might exhibit a better therapeutic effect. Highlights are as follows: 1. BMSCs repair lung injury induced by BLM. 2. BMSCs attenuate pulmonary fibrosis induced by BLM. 3. BMSCs transplantation down-regulates MMP9 and TIMP-1. 4. BMSCs transplantation down-regulates INF-γ and TGF-β. 5. Delayed transplantation timing of BMSCs might exhibit a better effect against BLM.
authors.affiliation: Department of Pulmonary Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shi-huan
authors.initials: SH
authors.lastname: Yu
authors.affiliation: Department of Pulmonary Disease, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Li-jie
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: Department of Pulmonary Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lv
authors.affiliation: Department of Pulmonary Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Chun-li
authors.initials: CL
authors.lastname: Che
authors.affiliation: Department of Pulmonary Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Da-ping
authors.initials: DP
authors.lastname: Fan
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Li-feng
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Department of Pulmonary Disease, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yi-mei
authors.initials: YM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D001761:Bleomycin; D001853:Bone Marrow / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D055370:Lung Injury / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D007371:Interferon-gamma; D020780:Matrix Metalloproteinase 9
keywords: BMSCs; INF-γ; MMP9; TGF-β; TIMP-1; pulmonary fibrosis