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Integrin-linked kinase (ILK) in pulmonary fibrosis

Abstract

Pulmonary fibrosis is a common feature of a large group of lung diseases. The molecular mechanisms underlying pulmonary fibrosis and the key macromolecules involved are not fully understood yet. In an effort to better understand aspects of pulmonary fibrosis, the established bleomycin injection model in mice was used and the focus of the present study was on integrin-linked kinase (ILK) expression. ILK is an intracellular protein involved in the regulation of integrin-mediated processes. In fibrosis, ILK has been examined in the kidney and in the liver where it mediates epithelial to mesenchymal transition (EMT) and hepatic stellate cell activation, respectively. However, information on ILK’s involvement in lung fibrosis is missing. In order to examine ILK’s role in pulmonary fibrosis, we used both an in vivo and an in vitro approach. In vivo, the bleomycin model was used in order to examine ILK’s expression and localization in the fibrotic lung. In vitro, transforming growth factor-β1 was used to induce fibrotic characteristics and EMT in alveolar epithelial cells. ILK’s role in alveolar EMT was studied by siRNA. Our results demonstrate that in the animal model used, ILK exhibits a decrease in expression at early stages of the fibrotic process and that a specific subset of fibroblasts is expressing ILK. The in vitro experiments suggested that ILK is not directly involved in E-cadherin downregulation and initiation of EMT (as is the case in renal fibrosis) but is involved in upregulation of vimentin. These results suggest that ILK is involved in lung fibrosis in a tissue-specific manner and raise the possibility to use it as a specific therapeutic target for lung fibrosis in the future.

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Acknowledgments

The present work was supported by funds from Biomedical Research Foundation of the Academy of Athens and PENED 03ED245 from the Greek Secretariat for Research and Technology. We are grateful to Dr. Stavros Giaglis for help with RT-RT-PCR, Dr. Stamatis N. Pagakis and Dr. Eleni Rigana for their help with confocal microscopy, Anna Agapaki for help with histological techniques, and to the members of Department of Histology for the excellent cooperation. We are also thankful to Dr. Dimitrios Kouretas for his support and interaction.

Declaration of interest

The authors declare they have no conflict of interest.

Author information

Correspondence to Aristidis S. Charonis.

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Kavvadas, P., Kypreou, K.P., Protopapadakis, E. et al. Integrin-linked kinase (ILK) in pulmonary fibrosis. Virchows Arch 457, 563–575 (2010). https://doi.org/10.1007/s00428-010-0976-7

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Keywords

  • Lung
  • Fibrosis
  • ILK
  • EMT