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WNT Signaling in Lung Disease

A Failure or a Regeneration Signal?

¹ Comprehensive Pneumology Center, Ludwig Maximilians University and Helmholtz Zentrum München, Institute of Lung Biology and Disease, Munich, Germany

Correspondence and requests for reprints should be addressed to Melanie Königshoff, M.D., Ph.D., Comprehensive Pneumology Center, Ludwig Maximilians University München and Helmholtz Zentrum München, Institute of Lung Biology and Disease, Ingolstädter Landstraße 1, München 85764, Germany. E-mail: melanie.koenigshoff{at}helmholtz-muenchen.de

The WNT family of signaling proteins is essential to organ development in general and lung morphogenesis in particular. Originally identified as a developmentally active signaling pathway, the WNT pathway has recently been linked to the pathogenesis of important lung diseases, in particular lung cancer and pulmonary fibrosis. This review summarizes our current understanding about WNT signaling in lung development and disease, and is structured into three chapters. The first chapter presents an introduction to WNT signaling, outlining WNT proteins, their receptors and signaling intermediates, as well as the regulation of this complex pathway. The second chapter focuses on the role of WNT signaling in the normal embryonic and adult lung, and highlights recent findings of altered WNT signaling in lung diseases, such as lung cancer, pulmonary fibrosis, or pulmonary arterial hypertension. In the last chapter, we will discuss novel data and ideas about the biological effects of WNT signaling on the cellular level, highlighting pleiotropic effects induced by WNT ligands on distinct cell types, and how these cellular effects may be relevant to the pathogenesis of the aforementioned diseases.

Key Words: β-catenin • epithelial cell • lung cancer • lung fibrosis • epithelial-to-mesenchymal transition

CLINICAL RELEVANCE This review summarizes our current understanding about WNT signaling in lung development and disease. We discuss novel data and ideas about the biological effects of WNT signaling on the cellular level, highlighting pleiotropic effects induced by WNT ligands on distinct cell types, and how these cellular effects may be relevant to the pathogenesis of the aforementioned diseases.

 

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