Castilla A, Prieto J, Fausto N
Department of Internal Medicine, University of Navarra, Pamplona, Spain.
N Engl J Med. 1991 Apr 4;324(14):933-40. doi: 10.1056/NEJM199104043241401.
Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation of unknown pathogenesis. Transforming growth factor (TGF) beta 1 induces the production of extracellular matrix proteins by liver cells and has been implicated in the pathogenesis of hepatic fibrosis in laboratory animals. TGF alpha is a hepatocyte mitogen that participates in liver regeneration.
Using Northern blot analysis, we studied the expression of TGF beta 1 messenger RNA (mRNA) in liver specimens from 42 patients with chronic hepatitis and cirrhosis and 12 subjects with either normal or fatty livers. The results were correlated with measurements of procollagen Type I mRNA in liver tissue, procollagen Type III peptide in serum, and the degree of histologic injury. We also investigated whether TGF alpha mRNA would be detectable in biopsy specimens of livers with proliferative activity.
TGF beta 1 mRNA expression correlated closely with the expression of procollagen Type I mRNA (r = 0.94) and serum procollagen Type III peptide (r = 0.89) and with the histologic activity index (r = 0.73). All patients with increased fibrogenic activity (serum procollagen Type III peptide level, greater than 11.9 micrograms per liter) had increased levels of TGF beta 1 mRNA (2 to 14 times the levels in the control group or in patients with normal fibrogenic activity), and both TGF alpha and H3 histone (a marker of DNA synthesis) mRNAs were detectable in patients with regenerative nodules. Six of eight patients with hepatitis C treated with interferon alfa for one year had sustained clinical responses with normalization of serum procollagen Type III peptide and aminotransferase activity. All these patients had normal levels of TGF beta 1 mRNA in liver specimens obtained at the end of the year.
TGF beta 1 may have an important role in the pathogenesis of fibrosis in patients with chronic liver disease, and TGF alpha expression may be associated with liver regeneration in these patients.
肝硬化是一种病因不明的肝纤维化和再生结节形成的弥漫性过程。转化生长因子（TGF）β1可诱导肝细胞产生细胞外基质蛋白，并在实验动物肝纤维化的发病机制中发挥作用。TGFα是一种肝细胞有丝分裂原，参与肝脏再生。
我们采用Northern印迹分析，研究了42例慢性肝炎和肝硬化患者以及12例正常或脂肪肝患者肝脏标本中TGFβ1信使核糖核酸（mRNA）的表达。结果与肝组织中I型前胶原mRNA、血清III型前胶原肽的检测结果以及组织学损伤程度相关。我们还研究了在具有增殖活性的肝脏活检标本中是否能检测到TGFα mRNA。
TGFβ1 mRNA表达与I型前胶原mRNA表达（r = 0.94）、血清III型前胶原肽（r = 0.89）以及组织学活性指数（r = 0.73）密切相关。所有纤维生成活性增加的患者（血清III型前胶原肽水平大于11.9微克/升），其TGFβ1 mRNA水平均升高（是对照组或纤维生成活性正常患者水平的2至14倍），并且在再生结节患者中可检测到TGFα和H3组蛋白（DNA合成标志物）的mRNA。8例接受干扰素α治疗一年的丙型肝炎患者中有6例出现持续临床反应，血清III型前胶原肽和转氨酶活性恢复正常。在年底获取的肝脏标本中，所有这些患者的TGFβ1 mRNA水平均正常。
TGFβ1可能在慢性肝病患者纤维化的发病机制中起重要作用，而TGFα表达可能与这些患者的肝脏再生有关。
