RGD Reference Report - Coexpression of Smad7 and UPA attenuates carbon tetrachloride-induced rat liver fibrosis. - Rat Genome Database

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Coexpression of Smad7 and UPA attenuates carbon tetrachloride-induced rat liver fibrosis.

Authors: Wang, B  Li, W  Chen, Y  Wang, Y  Sun, C  Chen, Y  Lu, H  Fan, J  Li, D 
Citation: Wang B, etal., Med Sci Monit. 2012 Oct;18(10):BR394-401.
RGD ID: 7241553
Pubmed: PMID:23018346   (View Abstract at PubMed)
PMCID: PMC3560566   (View Article at PubMed Central)

BACKGROUND: There is a great need for developing novel therapies to treat liver fibrosis. Previous studies showed that both Smad7 and uPA were inhibitors of liver fibrosis. Therefore, we explored the therapeutic effects of combinational gene therapy with Smad7 and uPA on CCl4-induced liver fibrosis. MATERIAL/METHODS: Smad7 and uPA genes were cloned into an adenovirus vector. To observe the therapeutic effects of coexpression of Smad7 and uPA genes, the recombinant adenovirus were delivered into CCL4-induced fibrosis models. Fibrillar collagen, hydroxyproline, alpha-SMA, TGF-beta1, MMP-13, TIMP-1, HGF and PCNA were detected to evaluate the fibrosis and to explore the mechanisms underlying the treatment with Smad7 and uPA. RESULTS: The results showed that single Smad7 or uPA adenovirus reduced CCL4 induced liver fibrosis significantly; while combination of Smad7 and uPA had more significant therapeutic effect on CCl4 induced liver fibrosis. Then the markers underlying the therapeutic effect of combination of Smad7 and uPA were also explored. Over-expression of Smad7 and uPA inhibited the expression of alpha-SMA and TGF- beta1 significantly. Combinational gene therapy also enhanced extracellular matrix degradation by increasing the expression of MMP-13, inhibiting TIMP-1 expression, and promoted hepatocyte proliferation, while single Smad7 or uPA only induced part of these changes. CONCLUSIONS: These results suggest that combinational gene therapy with Smad7 and uPA inhibited CCl4-induced rat liver fibrosis by simultaneously targeting multiple pathogenic pathways.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Cirrhosis treatmentISOPlau (Rattus norvegicus)7241553; 7241553 RGD 
Experimental Liver Cirrhosis treatmentIMP 7241553 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal liver morphology treatmentIMP 7241553 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Plau  (plasminogen activator, urokinase)

Genes (Mus musculus)
Plau  (plasminogen activator, urokinase)

Genes (Homo sapiens)
PLAU  (plasminogen activator, urokinase)


Additional Information