Epithelial cells are constitutively polarized to play fundamental functions such as vectorial transport. There are two membrane domains of epithelial cells, the apical membrane and basolateral membrane. A number of membrane proteins show asymmetric distribution in the plasma membrane in epithelial cells. On the other hand, the differences in lipid profile between the apical membrane and the basolateral membrane are less understood. Moreover, physiological meanings of lipid polarity remain unclear. In this research project, I try to define the roles of lipid asymmetry in the establishment of epithelial polarity and in the formation of epithelial-tube.

I recently developed a new method to determine the lipid composition of plasma membrane (Ikenouchi et al. 2012). Taking advantage of this method, I succeeded in clarifying the difference of lipid composition between the apical membrane and the basolateral membrane. Furthermore, by comparing the lipid profile between epithelial cells and mesenchymal cells, I identified several lipid species as epithelial-cell specific lipids. In this research project, I try to elucidate functional roles of these lipids by examining whether knock-down of biosynthetic enzymes in cultured epithelial cells affect epithelial polarity and epithelial-tube morphogenesis.

Most of studies concerning epithelial polarity and tubulogenesis have been focused on the elucidation of protein-protein interactions among polarity proteins. Although lipids are the main component of cells together with proteins, the functions of lipids or the physiological meaning of diversity of lipid species are not well elucidated. The aim of this project from the viewpoint of basic science is to clarify the importance of individual lipid species by using epithelial tube morphogenesis as an experimental model. The research purpose of this project for clinical science is to find novel therapeutic targets in diseases correlated with epithelial-polarity disorders and epithelial-mesenchymal transition, such as cancer, polycystic kidney disease and pulmonary fibrosis.