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

• Published in: BMC gastroenterology Vol. 9; no. 1; p. 81
• Main Authors: del Pilar Alatorre-Carranza, María, Miranda-Díaz, Alejandra, Yañez-Sánchez, Irinea, Pizano-Martínez, Oscar, Hermosillo-Sandoval, José M, Vázquez-Del Mercado, Mónica, Hernández-Hoyos, Sebastián, Martínez-Abundis, Ricardo, Fafutis-Morris, Mary, Segura-Ortega, Jorge, Delgado-Rizo, Vidal
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31-10-2009; BioMed Central; BMC
• Subjects: Adolescent; Adult; Aged; Biopsy; Cholestasis - complications; Cholestasis - genetics; Cholestasis - metabolism; Disease Progression; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins - biosynthesis; Extracellular Matrix Proteins - genetics; Female; Gene Expression; Humans; Liver - pathology; Liver Cirrhosis - etiology; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Smad7 Protein - biosynthesis; Smad7 Protein - genetics; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - genetics; Young Adult
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/1471-230X-9-81

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).
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.
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.