Schistosoma mansoni: Egg-induced downregulation of hepatic stellate cell activation and fibrogenesis
Schistosoma mansoni: Egg-induced downregulation of hepatic stellate cell activation and fibrogenesis
复制标题
DOI：
10.1016/j.exppara.2009.12.009
复制
发表时间：
2010-04-01
影响因子：
2.1
通讯作者：
Allen, Jeremy
中科院分区：
文献类型：
--
作者：
Anthony, Barrie;Mathieson, William;Allen, Jeremy
曼氏血吸虫卵被困在人类肝脏中可导致纤维化。由于肝纤维化需要激活肝星状细胞（HSC）从静止到成肌纤维细胞表型，我们研究了S。使用与人HSC的体外共培养物，对曼氏曼氏卵在该过程中的作用进行了研究，并评估了已建立的活化和纤维化的生物标志物。HSC显示α-平滑肌肌动蛋白（p < 0.001）、结缔组织生长因子（p < 0.01）和I型胶原（p < 0.001）的表达显著降低，但过氧化物酶体增殖物激活受体-γ（p < 0.01）的表达显著增加。在形态学上，HSC表现出细长的细细胞突起和减小的尺寸，增加的脂滴积累和减少的α-平滑肌肌动蛋白和F-肌动蛋白应力纤维的表达和组织。此外，巨噬细胞卵阻止了HSC对外源性转化生长因子-P的纤维化反应。总之，巨噬细胞卵阻断了HSC中的纤维化，这一发现可能对我们理解S.曼氏感染。(C)2010年爱思唯尔公司All rights reserved.
Eggs of Schistosoma mansomi trapped in human liver can lead to fibrosis. Since liver fibrosis requires activation of hepatic stellate cells (HSC) from a quiescent to a myofibroblastic phenotype, we investigated the effects of S. mansoni eggs on this process using in vitro co-cultures with human HSC and evaluated established biomarkers for activation and fibrosis. HSC demonstrate significantly reduced expression of alpha-smooth muscle actin (p < 0.001), connective tissue growth factor (p < 0.01) and type I collagen (p < 0.001) but significantly increased expression of peroxisome proliferator-activated receptor-gamma (p < 0.01). Morphologically, HSC exhibited elongated fine cellular processes and reduced size, increased accumulation of lipid droplets and reduced expression and organization of alpha-smooth muscle actin and F-actin stress fibres. Additionally, schistosome eggs prevented the HSC fibrogenic response to exogenous transforming growth factor-P. In summary, schistosome eggs blocked fibrogenesis in HSC, a finding which may have implications for our understanding of the fibrotic pathology in S. mansoni infections. (C) 2010 Elsevier Inc. All rights reserved.