Identification of transforming growth factors actively transcribed during the progress of liver fibrosis in biliary atresia
Identification of transforming growth factors actively transcribed during the progress of liver fibrosis in biliary atresia
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DOI：
10.1016/j.jpedsurg.2004.01.030
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发表时间：
2004-05-01
影响因子：
2.4
通讯作者：
Chen, CL
中科院分区：
文献类型：
--
作者：
Lee, SY;Chuang, JH;Chen, CL
背景/目的：转化生长因子-β（TGF-β）1和2及其受体TbetaR-I、TbetaR-II和TbetaR-III是体内强有力的促纤维化介质。它们的表达尚未完全阐明肝纤维化与胆道闭锁（BA）的进展。方法：作者比较了3例BA患者在加塞手术（KP）和3例肝移植（LT）中的肝细胞因子表达。来自没有肝脏疾病的儿童的两个肝脏样品作为正常对照（CO）。实时定量逆转录聚合酶链反应（QRT-PCR）用于确认TGF-β 1和2及其受体的相对mRNA表达的结果。采用免疫组化和酶联免疫分析（ELISA）技术对肝细胞TGF-β 2表达进行定位，并对各组间TGF-β 2蛋白表达进行定量分析。结果：与对照组相比，KP和LT患者肝纤维化进展过程中肝组织TGF-β 1和TGF-β 2 mRNA表达均增加。与KP和CO相比，仅TGF-β 2在LT中的表达显著增加（TGF-β 2 P = 0.001，TGF-β 1 P = 0.054）。TbetaR-I和TbetaR-II在组间均无显著变化;与CO相比，LT中TbetaR-III显著降低（P =.011）。TGF-β 2免疫染色主要定位于胆管上皮，LT中显著较高，其中增殖的胆管和肝细胞有助于免疫染色的增加，并且可能导致LT中血浆TGF-β 2蛋白水平显著高于KP。本研究确定了TGF-β 2是BA肝纤维化过程中转录最活跃的TGF-β基因，并发现TGF-β 2的上调与BA肝纤维化的发生、发展有相互关系。β 2与LT中TbetaR-III下调。
Background/Purpose: Transforming growth factor-beta (TGF-beta) 1 and 2 and their receptors TbetaR-I, TbetaR-II, and TbetaR-III are powerful profibrogenic mediators in the body. Their expression has not been completely elucidated in the progress of liver fibrosis associated with biliary atresia (BA).Methods: The authors compared the cytokine expression in the liver of 3 patients with BA at Kasai's procedure (KP) and in 3 patients at liver transplantation (LT). Two liver samples from children with no liver disorders served as normal controls (CO). Real-time quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) was used to confirm the findings of relative mRNA expression of TGF-beta1 and 2 and their receptors. An immunohistochemistry and an enzyme-linked immunoassay (ELISA) were used to localize the liver cells that express TGF-beta2 and to quantitate the protein expression among groups.Results: Compared with controls, both TGF-beta1 and TGF-beta2 mRNA expression increased in the liver during the progress of liver fibrosis in patients with KP and LT on the array. Only TGF-beta2 showed a significant increase in expression in LT compared with KP and CO (P =.001 for TGF-beta2 and P = 0.054 for TGF-beta1). Both TbetaR-I and TbetaR-II showed no significant change among groups; TbetaR-III decreased significantly in LT compared with CO (P =.011). TGF-beta2 immunostaining was mainly localized in the bile duct epithelium and was remarkably higher in LT in which the proliferating bile ductules and the hepatocytes contributed to the increase in immunostaining and possibly to significantly higher plasma TGF-beta2 protein levels in LT than in KP.Conclusions: This study identified TGF-beta2 as the most actively transcribed TGF-beta gene during the progress of liver fibrosis in BA and found a reciprocal relationship of upregulation of TGF-beta2 with downregulation of TbetaR-III in LT.