title: Effect of antisense TIMP-1 cDNA on the expression of TIMP-1 and MMP-2 in lung tissue with pulmonary fibrosis induced by bleomycin.
abstract: The aim of this study was to observe the effect of antisense tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) cDNA on the concentration of hydroxyproline (HYP) and the expression of TIMP-1 and matrix metalloproteinase-2 (MMP-2) in the lung tissue of rats with bleomycin (BLM)‑induced pulmonary fibrosis. Sprague-Dawley rats were randomly divided into 5 groups: the control, pulmonary fibrosis model, sense TIMP-1 transfection, antisense TIMP-1 transfection and empty vector transfection groups. For the transfection groups, following the intratracheal injection of BLM on days 1, 3, 7, 14, 28 and 60, the rats were treated with retroviral vectors and sacrificed on day 28. The control and pulmonary fibrosis groups were treated with normal saline at the same time‑points. The concentration of HYP and the expression levels of TIMP-1 and MMP-2 in the lung tissue were detected. The HYP concentration and lung tissue TIMP-1 expression levels of the antisense TIMP-1 group decreased significantly on days 1 and 3 compared with those of the empty vector and pulmonary fibrosis groups at the same time-points (P<0.01), but increased significantly in the sense TIMP-1 group (P<0.01). No significant differences were observed in the HYP concentration and TIMP-1 expression levels in the antisense TIMP-1, sense TIMP-1, empty vector and pulmonary fibrosis groups on days 7, 14, 28 and 60. The lung expression levels of MMP-2 in all groups, with the exception of the control group, had no significant differences at all time-points (P>0.05). Antisense TIMP-1 cDNA retroviral vectors are able to suppress the development of pulmonary fibrosis in the early stages.
authors.affiliation: Department of Respiratory Medicine, The First Afﬁliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Tang
authors.forename: Jingwei
authors.initials: J
authors.lastname: Mao
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Taihua
authors.initials: T
authors.lastname: Wu
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D016373:DNA, Antisense / Q000235:genetics*; D005786:Gene Expression Regulation; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016373:DNA, Antisense; D019715:Tissue Inhibitor of Metalloproteinase-1; D001761:Bleomycin; D019716:Tissue Inhibitor of Metalloproteinase-2