Abstract
Purpose: Biliary atresia (BA) is the most common indication of liver transplantation in - children. Pathogenesis of hepatic fibrosis, which is a prominent feature of BA, remains obscure. The purpose of this work was to determine the cellular sources of transforming growth factor beta- 1 (TGF beta 1) and establish the relationship between TGF beta 1-producing cells and extracellular matrix producing myofibroblasts (MFBs) in advanced BA.
Methods: Trichrome staining and immunohistochemistry were carried out to determine the expression pattern of collagen and TGF beta 1 protein in explant liver specimens from patients with BA. The intensities of portal and lobular TGF beta 1 expressions were compared. - Immunofluorescence technique was carried out to determine the relationship between alpha-smooth muscle actin (alpha-SMA)-positive-MFB and TGF beta 1-positve cells.
Results: Lobular TGF beta 1 protein expression was significantly higher than portal (89 +/- 6 versus 10 +/- 1 arbitrary units, P <= 0.05), whereas no difference was noted in livers used as control (10 +/- 1.6 versus 19 +/- 5 arbitrary units, P = 0.11). TGF beta 1 expression was more in the center of nodules versus MFB in surrounding fibrous septa. Contrary to TGF beta 1 expression, alpha 1-SMA was mostly expressed in the portal structures and the adjacent fibrous septa enacting lobulation of the parenchyma. The results obtained by coimmunofluorescence staining showed no colocalization of alpha-SMA and TGF beta 1.
Conclusions: TGF beta 1 protein expression is mostly localized to hepatocytes in advanced BA. These findings suggest a paracrine mechanisms of TGF beta 1-driven fibrogenesis in advanced BA.