Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-β and extracellular matrix proteins
1 Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara; Sierra Mojada 950, Col. Independencia, Guadalajara, Jalisco 44340 México
2 Hospital de Especialidades Centro Médico Nacional de Occidente, IMSS; Belisario Domínguez 1000, Col. Independencia, Guadalajara, Jalisco 44340 México
3 Instituto de Investigación en Reumatología y Sistema Músculo Esquelético (IIRSME), Universidad de Guadalajara; Sierra Mojada 950, Col. Independencia, Guadalajara, Jalisco 44340 México
4 Servicio de Gastroenterología Hospital Civil de Guadalajara, Universidad de Guadalajara, Hospital 278, Col. El Retiro, Guadalajara, Jalisco 44280 México
5 Departamento de Reumatología, Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Universidad de Guadalajara, Salvador Quevedo y Zubieta 750, Col. Independencia, Guadalajara, Jalisco 44340 México
BMC Gastroenterology 2009, 9:81 doi:10.1186/1471-230X-9-81Published: 31 October 2009
Liver fibrosis is the result of continuous liver injury stemming from different etiological factors. Bile duct injury induces an altered expression of TGF-β, 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-β signaling. The aim of the study was to determine whether Smad7 mRNA expression correlates with the gene expression of TGF-β, Col I, Col III, Col IV, or PAI-1 in liver fibrosis secondary to bile duct injury (BDI).
Serum TGF-β 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-β concentration, Col I and Col III expression, and the amount of fibrosis.
We found augmented serum concentration of TGF-β 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-β, 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-β concentration and Smad7 mRNA expression.