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《Current Immunology》 2015-06
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Effect of osteopontin on the expression of MMP-9/TIMP-1 and typeⅠ/Ⅲ collagen mRNA in the lung tissue of rats with bleomycin-induced pulmonary fibrosis

ZENG Ming;ZHANG Yu-kun;WU Yong-chang;JIANG Bing;LIU Dan;Department of Respiratory Medicine,The Yongchuan hospital affiliated to Chongqing medical university;Department of Radiology,The Yongchuan hospital affiliated to Chongqing medical university;  
To investigate the influence of osteopontin on the expression of MMP-9/TIMP-1and typeⅠ/Ⅲ collagen mRNA in lung tissue of rats with bleomycin-induced pulmonary fibrosis seventy-two adult female Wistar rats were randomly divided into3groups:the model(bleomycin(BLM)group,the anti-osteopontin antibody(OPN-Ab)group,and the normal group.Animals of both the OPN-Ab group and the model group were intratracheally instilled with BLM,while the normal group with 0.9%NaCl solution.Taking intratracheally instillation as day 0,the OPN-Ab group was injected 0.5ml of anti-OPN antibody(1:32)at day 0,2,4and 6,while the control group and the model.Each of the 3groups were further divided into 3subgroups,which were sacrificed at day 7,14 and 28respectively.HE and Masson staining were performed to observe the extent of alveolits and fibrosis;OPN,matrix metalloproteinases-9(MMP-9),tissue inhibitors of metalloproteinases-1(TIMP-1)protein in the tissue of the left lung were assessed by immunohistochemistry;The mRNA levels ofⅠ/ Ⅲ collagen in the lung tissue were measured by RT-PCR.Compared with the model group,the scores of alveolitis in the OPN-Ab group were remarkably ameliorated at day7 and 14(P0.01),while the scores of fibrosis in the OPN-Ab group were significantly reduced(P0.05).The expression of OPN,MMP-9and TIMP-1protein in the lung tissue in the model group and the OPN-Ab group was obviously higher as compared with that in the control group(P0.01).The expression of OPN,MMP-9and TIMP-1protein in lung tissue in model group reached the highest at day 7,and then dropped,but still elevated over the control group at day 28(P0.01).Compared with those of BLM group,the level of OPN,MMP-9and TIMP-1protein in the lung tissue in OPN-Ab group were lower(P0.01).The mRNA levels of typeⅠ/Ⅲcollagen in OPN-Ab group were significantly lower than those in the control group(P0.05).Thus,OPN may play an important role in the pathogenesis of pulmonary fibrosis,and anti-OPN antibody could abate the alveolitis and the fibrosis in BLM-induced pulmonary fibrosis rats,which might attribute to inhibition of collagen and the decrease of MMP-9and TIMP-1in the lung tissue.
【Fund】: 重庆市卫生计生委医学科研项目20142060
【CateGory Index】: R563
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