Effects of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 on liver fibrosis in rats / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 192-197, 2005.
Article
de En
| WPRIM
| ID: wpr-257300
Bibliothèque responsable:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>No efficient therapy for liver fibrosis has been available. This study was aimed to provide evidence that the introduction of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 (TIMP-1) into a rat model of immunologically induced liver fibrosis can result in the increased activity of interstitial collagenase, thus enhancing the degradation of collagen.</p><p><b>METHODS</b>Real-time nested polymerase chain reaction (RT-Nested-PCR) and gene recombination techniques were used to construct a rat antisense TIMP-1 recombinant plasmid that can be expressed in eukaryotic cells. Both the recombinant plasmid and an empty vector (pcDNA3) were encapsulated with glycosyl-poly-L-lysine and injected into rats suffering from pig serum-induced liver fibrosis. The expression of exogenous transfected plasmid was assessed by Northern blot, RT-PCR, and Western blot. Hepatic interstitial collagenase activity was detected using fluorescinisothiocyanate (FITC)-labeled type I collagen. In addition to hepatic hydroxyproline content, hepatic collagen types I and III were detected by immunohistochemical staining, and the stages of liver fibrosis by Van Gieson staining.</p><p><b>RESULTS</b>Exogenous antisense TIMP-1 was successfully expressed in vivo and could block the gene and protein expression of TIMP-1. Active and latent hepatic interstitial collagenase activities were elevated (P < 0.01), hepatic hydroxyproline content and the accumulation of collagen types I and III were lowered, and liver fibrosis was alleviated in the antisense TIMP-1 group (P < 0.01) as compared with the model group.</p><p><b>CONCLUSION</b>The results demonstrate that antisense TIMP-1 recombinant plasmids have some inhibitory effect on liver fibrosis.</p>
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Plasmides
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Thérapeutique
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Éléments antisens (génétique)
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Rat Sprague-Dawley
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Collagenases
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Inhibiteur tissulaire de métalloprotéinase-1
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Utilisations thérapeutiques
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Génétique
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Hydroxyproline
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Foie
Limites du sujet:
Animals
langue:
En
Texte intégral:
Chinese Medical Journal
Année:
2005
Type:
Article