University Bordeaux, Laboratoire de bactériologie, F-33076 Bordeaux, France.
Eur J Cell Biol. 2012 Mar;91(3):161-70. doi: 10.1016/j.ejcb.2011.11.003. Epub 2012 Feb 3.
Helicobacter pylori (H. pylori) infection may contribute to many extragastric diseases including liver cirrhosis and hepatocellular carcinoma. However, the exact mechanism by which H. pylori induces the liver damage is largely unknown. We used cultured mouse primary hepatocytes as an in vitro model to investigate different aspects of liver physiology and pathology. In this study, we show that primary hepatocytes are able to assemble actin-based cytoskeletal structures called podosomes at the ventral plasma membrane. These structures are positive for podosome markers such as cortactin, vinculin and integrins and comprise proteolytic potential. Infection with the pathogen H. pylori further stimulates the formation of podosomes in primary hepatocytes. The use of pharmacological inhibitors reveals that this response is mediated, at least in part, by TGFβ, a cytokine known to regulate podosome formation in endothelial cells. Similar results are obtained with the hepatoma cell line Huh7. Podosome formation is associated with increased hepatocyte degrading capacities but also with reduced cell motility. Therefore, podosome assembly translates into hepatocyte malfunction. Our study supports the hypothesis that hepatocytes can also assemble podosomes under pathological conditions in vivo.
幽门螺杆菌（H. pylori）感染可能导致许多胃部以外的疾病，包括肝硬化和肝细胞癌。然而，H. pylori 诱导肝损伤的确切机制在很大程度上尚不清楚。我们使用培养的小鼠原代肝细胞作为体外模型，研究了肝脏生理学和病理学的不同方面。在这项研究中，我们表明原代肝细胞能够在腹侧质膜上组装称为足突的基于肌动蛋白的细胞骨架结构。这些结构对足突标志物（如桩蛋白、纽蛋白和整合素）呈阳性，并具有蛋白水解潜力。病原体 H. pylori 的感染进一步刺激原代肝细胞中足突的形成。使用药理抑制剂的研究表明，这种反应至少部分是由 TGFβ介导的，TGFβ是一种已知调节内皮细胞足突形成的细胞因子。在肝癌细胞系 Huh7 中也获得了类似的结果。足突的形成与肝细胞降解能力的增加有关，但也与细胞迁移能力的降低有关。因此，足突的组装导致了肝细胞功能障碍。我们的研究支持了这样一种假设，即在体内病理条件下，肝细胞也可以组装足突。
