Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-β and extracellular matrix proteins

BACKGROUND Liver fibrosis is the result of continuous liver injury stemming from different etiological factors. Bile duct injury induces an altered expression of TGF-beta, which has an important role in liver fibrosis because this cytokine induces the expression of target genes such as collagens, PAI-1, TIMPs, and others that lead to extracellular matrix deposition. Smad7 is the principal inhibitor that regulates the target gene transcription of the TGF-beta signaling. The aim of the study was to determine whether Smad7 mRNA expression correlates with the gene expression of TGF-beta, Col I, Col III, Col IV, or PAI-1 in liver fibrosis secondary to bile duct injury (BDI). RESULTS Serum TGF-beta concentration was higher in BDI patients (39 296 pg/ml) than in liver donors (9008 pg/ml). Morphometric analysis of liver sections showed 41.85% of tissue contained fibrotic deposits in BDI patients. mRNA expression of Smad7, Col I, and PAI-1 was also significantly higher (P < 0.05) in patients with BDI than in controls. Smad7 mRNA expression correlated significantly with TGF-beta concentration, Col I and Col III expression, and the amount of fibrosis. CONCLUSION We found augmented serum concentration of TGF-beta and an increase in the percentage of fibrotic tissue in the liver of BDI patients. Contrary to expected results, the 6-fold increase in Smad7 expression did not inhibit the expression of TGF-beta, collagens, and PAI-1. We also observed greater expression of Col I and Col III mRNA in BDI patients and significant correlations between their expression and TGF-beta concentration and Smad7 mRNA expression.