Effect of human amniotic epithelial cells on pro-fibrogenic resident hepatic cells in a rat model of liver fibrosis.
Effect of human amniotic epithelial cells on pro-fibrogenic resident hepatic cells in a rat model of liver fibrosis.
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人羊膜上皮细胞对肝纤维化大鼠模型中促纤维化肝细胞的影响。
DOI：
10.1111/jcmm.13396
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Parolini O
中科院分区：
文献类型：
--
作者：
Cargnoni A;Farigu S;Cotti Piccinelli E;Bonassi Signoroni P;Romele P;Vanosi G;Toschi I;Cesari V;Barros Sant'Anna L;Magatti M;Silini AR;Parolini O
肌成纤维细胞是导致纤维化病变特征性细胞外基质过度合成的关键纤维发生细胞。在肝纤维化中，肌成纤维细胞来源于肝星状细胞（HSC）和门静脉成纤维细胞（PF）的活化，或来源于经历上皮-间充质转化的小管上皮细胞的成纤维细胞的活化。导管细胞还可以通过α v β 6整联蛋白激活TGF-β（主要的纤维化生长因子）间接促进肌成纤维细胞的生成。此外，肝损伤后，肝窦细胞可能失去维持HSC静止的能力，从而有利于HSC向肌成纤维细胞分化。羊膜及其衍生的上皮细胞（hAEC）已显示降低患有肝纤维化的啮齿动物中的肝肌成纤维细胞水平。在这项研究中，在大鼠肝纤维化模型中，我们研究了hAEC对有助于肌成纤维细胞生成的驻留肝细胞的影响。我们的数据表明，hAEC减少肌成纤维细胞的数量，从而减少纤连蛋白和胶原蛋白沉积。有趣的是，我们发现hAEC强烈作用于特定的肌成纤维细胞前体。具体地，hAEC减少PF而不是HSC的活化。此外，hAEC通过抑制其增殖和α v β 6整合素表达靶向反应性小管细胞，从而降低TGF-β活化。此外，hAEC抵消了小管细胞向成纤维细胞的转变，而它不影响损伤诱导和纤维化促进的窦状隙变化。总之，在新出现的治疗应用中，hAEC在肝脏疾病中，其对PF和导管细胞的特异性作用强烈表明其在肝损伤中的应用，涉及门静脉室的扩张和激活。
Myofibroblasts are key fibrogenic cells responsible for excessive extracellular matrix synthesis characterizing the fibrotic lesion. In liver fibrosis, myofibroblasts derive either from activation of hepatic stellate cells (HSC) and portal fibroblasts (PF), or from the activation of fibroblasts that originate from ductular epithelial cells undergoing epithelial–mesenchymal transition. Ductular cells can also indirectly promote myofibroblast generation by activating TGF‐β, the main fibrogenic growth factor, through αvβ6 integrin. In addition, after liver injury, liver sinusoidal cells can lose their ability to maintain HSC quiescence, thus favouring HSC differentiation towards myofibroblasts. The amniotic membrane and epithelial cells (hAEC) derived thereof have been shown to decrease hepatic myofibroblast levels in rodents with liver fibrosis. In this study, in a rat model of liver fibrosis, we investigated the effects of hAEC on resident hepatic cells contributing to myofibroblast generation. Our data show that hAEC reduce myofibroblast numbers with a consequent reduction in fibronectin and collagen deposition. Interestingly, we show that hAEC strongly act on specific myofibroblast precursors. Specifically, hAEC reduce the activation of PF rather than HSC. In addition, hAEC target reactive ductular cells by inhibiting their proliferation and αvβ6 integrin expression, with a consequent decrease in TGF‐β activation. Moreover, hAEC counteract the transition of ductular cells towards fibroblasts, while it does not affect injury‐induced and fibrosis‐promoting sinusoidal alterations. In conclusion, among the emerging therapeutic applications of hAEC in liver diseases, their specific action on PF and ductular cells strongly suggests their application in liver injuries involving the expansion and activation of the portal compartment.
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影响因子：
13.5
作者：
DeLeve, Laurie D.
通讯作者：
DeLeve, Laurie D.
影响因子：
4.2
作者：
Fabris L;Strazzabosco M
通讯作者：
Strazzabosco M
影响因子：
15.9
作者：
Omenetti, Alessia;Porrello, Alessandro;Diehl, Anna Mae
通讯作者：
Diehl, Anna Mae
影响因子：
29.4
作者：
Knittel, T;Kobold, D;Ramadori, G
通讯作者：
Ramadori, G
DOI：
10.1016/j.biocel.2009.03.010
发表时间：
2009-11-01
影响因子：
4
作者：
Novo, Erica;di Bonzo, Lorenzo Valfre;Parola, Maurizio
通讯作者：
Parola, Maurizio