Role of Wnt/β-Catenin Signaling in Epithelial Differentiation of Lung Resident Mesenchymal Stem Cells

Abstract

Accumulating evidence has demonstrated that stem cells have the ability to repair the lung tissue injuries following either injection of cultured cells or bone marrow transplantation. As a result, increasing attention has focused on the lung resident mesenchymal stem cells (LR-MSCs) for repairing damaged lung tissues. Meanwhile, some studies have revealed that Wnt/β-catenin signaling plays an important role in the epithelial differentiation of mesenchymal stem cells (MSCs). In the current study, our aim was to explore the roles of Wnt/β-catenin signaling on cell proliferation and epithelial differentiation of LR-MSCs. We have successfully isolated the stem cell antigen (Sca)-1(+) CD45(-) CD31(-) cells which were proposed to be LR-MSCs by magnetic-activated cell sorting (MACS). Furthermore, we demonstrated the expression of epithelial markers on LR-MSCs following indirect co-culture of these cells with alveolar epithelial type II (ATII) cells, confirming the epithelial phenotype of LR-MSCs following co-culture. In order to clarify the regulatory mechanisms of Wnt/β-catenin signaling in epithelial differentiation of LR-MSCs, we measured the protein levels of several important members involved in Wnt/β-catenin signaling in the presence or absence of some canonical activators and inhibitors of the β-catenin pathways. In conclusion, our study demonstrated that Wnt/β-catenin signaling may be an essential mechanism underlying the regulation of epithelial differentiation of LR-MSCs.