Transforming growth factor betas and their receptors in human liver cirrhosis

被引:32
作者
Baer, HU [1 ]
Friess, H [1 ]
Abou-Shady, M [1 ]
Berberat, P [1 ]
Zimmermann, A [1 ]
Gold, LI [1 ]
Korc, M [1 ]
Büchler, MW [1 ]
机构
[1] Univ Bern, Dept Visceral & Transplantat Surg, CH-3010 Bern, Switzerland
关键词
fibrogenesis; immunohistochemistry; liver cirrhosis; Northern blot analysis; transforming growth factor-beta; transforming growth factor-beta receptors;
D O I
10.1097/00042737-199812000-00009
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background Transforming growth factor betas (TGF-beta s) are a group of homologous polypeptides that exert pleiotropic effects on various cell types and stimulate the formation of extracellular matrix and fibrosis. To evaluate whether TGF-beta isoforms (TGF-beta 1, TGF-beta 2 and TGF-beta 3) and their receptors (types I-III) are also of importance in the pathophysiology of liver cirrhosis, we analysed their concomitant expression and localization in human liver cirrhosis. Patients Cirrhotic liver tissue samples were obtained from 17 patients (four women, 13 men) with a median age of 41 years (range 22-67). Normal liver tissues from ten patients (seven women, three men) with a median age of 55 years (range 45-75) served as controls. Methods The tissues were fixed in Bouin's solution and paraffin-embedded for histological analysis. For RNA analysis, freshly obtained tissue samples were snap-frozen in liquid nitrogen and stored at -80 degrees C until analysed. Northern blot analysis was used to examine the expression of TGF-beta 1, beta 2 and beta 3 and their receptors, type I (TPR-I), type II (TPR-II) and type III (TPR-III), Immunohistochemistry was performed to determine the localization of the corresponding proteins in the normal and the cirrhotic liver. Results Northern blot analysis revealed enhanced expression (P < 0.05) of TGF-beta 1 (twofold increase), TGF-beta 2 (threefold increase) and TGF-beta 3 (8.5-fold increase) and of TPR-II (threefold increase) mRNA in liver cirrhosis in comparison with normal controls. In contrast, T beta R-I (ALK-5) and T beta R-III mRNA expression showed no significant changes, No TGF-beta isoform immunoreactivity was present in hepatocytes in either normal livers or in liver cirrhosis. However, in liver cirrhosis, intense TGF-beta 1 immunoreactivity was present in bile duct and ductular epithelial cells (including ductular proliferations) and in inflammatory cells, In a few sinusoidal lining cells, faint TGF-beta 1 and moderate TGF-beta 2 immunoreactivity was present. TGF-beta 3 immunostaining was present in bile duct and ductular epithelial cells, in inflammatory cells and in fibroblast-like spindle cells in liver cirrhosis, For T beta R-I and T beta R-II, the immunoreactivity was localized in hepatocytes and biliary cells in normal and cirrhotic liver tissues, with higher intensity for T beta R-II in the cirrhotic liver. Conclusion Enhanced expression of all three TGF-beta isoforms and of T beta R-II in liver cirrhosis suggests their involvement in this fibrotic disorder. The higher immunoreactivity of the three TGF-beta isoforms in the bile duct epithelial cells in cirrhotic tissues suggests a possible role of these cells in the pathogenesis of liver cirrhosis, Eur J Gastroenterol Hepatol 10:1031-1039 (C) 1998 Lippincott Williams & Wilkins.
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页码:1031 / 1039
页数:9
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