Shi Chaowen, Lv Tengfei, Xiang Zou, Sun Zhaorui, Qian Weiping, Han Xiaodong
Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Nanjing, 210093, China.
Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
J Cell Biochem. 2015 Aug;116(8):1532-9. doi: 10.1002/jcb.25069.
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.
越来越多的证据表明，无论是注射培养细胞还是进行骨髓移植后，干细胞都具有修复肺组织损伤的能力。因此，人们越来越关注肺驻留间充质干细胞（LR-MSCs）在修复受损肺组织方面的作用。与此同时，一些研究表明，Wnt/β-连环蛋白信号通路在间充质干细胞（MSCs）的上皮分化中起重要作用。在本研究中，我们的目的是探讨Wnt/β-连环蛋白信号通路对LR-MSCs细胞增殖和上皮分化的作用。我们通过磁珠激活细胞分选（MACS）成功分离出干细胞抗原（Sca）-1（+）CD45（-）CD31（-）细胞，这些细胞被认为是LR-MSCs。此外，我们通过将这些细胞与肺泡II型上皮（ATII）细胞间接共培养，证实了LR-MSCs上上皮标志物的表达，从而确认了共培养后LR-MSCs的上皮表型。为了阐明Wnt/β-连环蛋白信号通路在LR-MSCs上皮分化中的调控机制，我们在存在或不存在β-连环蛋白通路的一些经典激活剂和抑制剂的情况下，测量了参与Wnt/β-连环蛋白信号通路的几个重要成员的蛋白水平。总之，我们的研究表明，Wnt/β-连环蛋白信号通路可能是LR-MSCs上皮分化调控的重要机制。
