title: TGF-β and TGF-β/Smad signaling in the interactions between Echinococcus multilocularis and its hosts.
abstract: 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.
authors: 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.
authors: Junhua
authors: J
authors: Wang
authors: Chuanshan
authors: C
authors: Zhang
authors: Xufa
authors: X
authors: Wei
authors: Oleg
authors: O
authors: Blagosklonov
authors: Guodong
authors: G
authors: Lv
authors: Xiaomei
authors: X
authors: Lu
authors: Georges
authors: G
authors: Mantion
authors: Dominique A
authors: DA
authors: Vuitton
authors: Hao
authors: H
authors: Wen
authors: Renyong
authors: R
authors: Lin
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004443:Echinococcosis; D004444:Echinococcosis, Hepatic / Q000235:genetics / Q000378:metabolism*; D048210:Echinococcus multilocularis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D051785:Smad Proteins; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse