State Key Lab Incubation Base of Xinjiang Major Diseases Research (2010DS890294) and Xinjiang Key Laboratory of Echinococcosis, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
PLoS One. 2013;8(2):e55379. doi: 10.1371/journal.pone.0055379. Epub 2013 Feb 6.
Alveolar echinococcosis (AE) is characterized by the development of irreversible fibrosis and of immune tolerance towards Echinococcus multilocularis (E. multilocularis). Very little is known on the presence of transforming growth factor-β (TGF-β) and other components of TGF-β/Smad pathway in the liver, and on their possible influence on fibrosis, over the various stages of infection. Using Western Blot, qRT-PCR and immunohistochemistry, we measured the levels of TGF-β1, TGF-β receptors, and down-stream Smads activation, as well as fibrosis marker expression in both a murine AE model from day 2 to 360 post-infection (p.i.) and in AE patients. TGF-β1, its receptors, and down-stream Smads were markedly expressed in the periparasitic infiltrate and also in the hepatocytes, close to and distant from AE lesions. Fibrosis was significant at 180 days p.i. in the periparasitic infiltrate and was also present in the liver parenchyma, even distant from the lesions. Over the time course after infection TGF-β1 expression was correlated with CD4/CD8 T-cell ratio long described as a hallmark of AE severity. The time course of the various actors of the TGF-β/Smad system in the in vivo mouse model as well as down-regulation of Smad7 in liver areas close to the lesions in human cases highly suggest that TGF-β plays an important role in AE both in immune tolerance against the parasite and in liver fibrosis.
泡型包虫病（AE）的特征是不可逆纤维化的发展和对多房棘球绦虫（E.multilocularis）的免疫耐受。对于转化生长因子-β（TGF-β）和 TGF-β/Smad 通路的其他成分在肝脏中的存在，以及它们在感染的各个阶段对纤维化的可能影响，我们知之甚少。我们使用 Western Blot、qRT-PCR 和免疫组织化学方法，在感染后第 2 天至 360 天的小鼠 AE 模型和 AE 患者中测量了 TGF-β1、TGF-β 受体和下游 Smads 激活以及纤维化标志物的表达水平。TGF-β1、其受体和下游 Smads 在寄生虫周围浸润物中以及靠近和远离 AE 病变的肝细胞中均有明显表达。在寄生虫周围浸润物中，在感染后 180 天出现明显纤维化，在远离病变的肝实质中也存在纤维化。在感染后的时间过程中，TGF-β1 的表达与 CD4/CD8 T 细胞比值相关，这一比值长期以来被描述为 AE 严重程度的标志。在体内小鼠模型中 TGF-β/Smad 系统的各种因子的时间过程以及在人类病例中靠近病变的肝区中 Smad7 的下调强烈表明，TGF-β 在 AE 中对寄生虫的免疫耐受和肝纤维化都具有重要作用。
