Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-beta 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.


CONCLUSIONS
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.
del Pilar Alatorre-Carranza
María
M
Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco 44340, México. pilyac@hotmail.com
Miranda-Díaz
Alejandra
A
Yañez-Sánchez
Irinea
I
Pizano-Martínez
Oscar
O
Hermosillo-Sandoval
José M
JM
Vázquez-Del Mercado
Mónica
M
Hernández-Hoyos
Sebastián
S
Martínez-Abundis
Ricardo
R
Fafutis-Morris
Mary
M
Segura-Ortega
Jorge
J
Delgado-Rizo
Vidal
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002779:Cholestasis / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051906:Smad7 Protein / Q000096:biosynthesis / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta