Helicobacter infection induces podosome assembly in primary hepatocytes in vitro

Eur J Cell Biol. 2012 Mar;91(3):161-70. doi: 10.1016/j.ejcb.2011.11.003. Epub 2012 Feb 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / pathology
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • Benzamides / pharmacology
  • Cell Line, Tumor
  • Dioxoles / pharmacology
  • Helicobacter Infections / metabolism*
  • Helicobacter Infections / pathology*
  • Helicobacter pylori*
  • Hepatocytes / microbiology
  • Hepatocytes / pathology*
  • Hepatocytes / ultrastructure
  • Humans
  • Imidazoles / pharmacology
  • Liver / metabolism
  • Liver / pathology
  • Liver / ultrastructure
  • Mice
  • Primary Cell Culture
  • Quinoxalines / pharmacology
  • Transforming Growth Factor beta / metabolism

Substances

  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • 6-(2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline
  • Benzamides
  • Dioxoles
  • Imidazoles
  • Quinoxalines
  • Transforming Growth Factor beta