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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
Author(s) -
Yu Shihuan,
Liu Lijie,
Lv Bin,
Che Chunli,
Fan Daping,
Wang Lifeng,
Zhang Yimei
Publication year - 2015
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3118
Subject(s) - bleomycin , pulmonary fibrosis , medicine , mesenchymal stem cell , fibrosis , transplantation , bone marrow , hydroxyproline , lung , inflammation , pathology , stem cell , biology , chemotherapy , genetics
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 β 1 (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. Copyright © 2015 John Wiley & Sons, Ltd. Highlights are as follows: BMSCs repair lung injury induced by BLM. BMSCs attenuate pulmonary fibrosis induced by BLM. BMSCs transplantation down‐regulates MMP9 and TIMP‐1. BMSCs transplantation down‐regulates INF‐ γ and TGF‐ β . Delayed transplantation timing of BMSCs might exhibit a better effect against BLM.