[mRNA expression of matrix metalloproteinase-2 and membrane type matrix metalloproteinase in pulmonary fibroblasts and macrophages of rat pulmonary fibrosis model].
OBJECTIVE
To study the changes and significance of MMP-2 and MT1-MMP mRNA expressions in fibroblasts and macrophages of rat pulmonary fibrosis model.


METHODS
Fifty pathogen-free Sprague-Dawley rats were randomly divided into ten groups. Five groups were instillated with bleomycin A5 (BLM A5) intratracheally, while 5 control groups with normal saline instead. Pulmonary interstitial fibroblasts and alveolar macrophages were isolated at day 1,3,7,14,28th after BLM exposure. The mRNA expression of MMP-2 and MT1-MMP was evaluated by RT-PCR quantitative analysis.


RESULTS
(1) The MMP-2 gene expression of fibroblasts increased 2.05 times(t = 10.667, P < 0.01) higher than that of control in 24 hours after bleomycin instillation and remained at the high level until the 28th day after exposure. It was only slightly increased in macrophages at the first day (t = 3.27, P < 0.05) and dropped down to the level of control during pulmonary fibrosis. (2) The mRNA expressions of MT1-MMP were enhanced both in fibroblasts and macrophages of fibrosis groups. They were 2.1 times(t = 4.823, P < 0.01) higher than that of control at the 14th day and 1.8 times(t = 4.016, P < 0.01) at the 28th day, respectively, in fibroblasts, while it was 2.4 times(t = 5.851, P < 0.01) higher than that of control at the 28th day in macrophages.


CONCLUSIONS
(1) Fibroblasts not only were the target cells but also involved in the damage of the pulmonary basement membrane and in the initiation of pulmonary fibrosis mediated by up-regulation of the mRNA expression of MMP-2. (2) The highly expressed MT1-MMP of fibroblasts and macrophages in the late stage of pulmonary fibrosis participated in the activation of pro-MMP-2 to promote the progression of pulmonary fibrosis.
Lu
S
S
Department of Pathology, Medical School of Fudan University, Shanghai 200032, China.
Zhang
N
N
Zhang
X
X
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D001761:Bleomycin; C025703:bleomycetin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2