PM2.5 collecting in a tire manufacturing plant affects epithelial differentiation of human umbilical cord derived mesenchymal stem cells by Wnt/β-catenin pathway

摘要

Mesenchymal stem cells (MSCs) can differentiate into pulmonary epithelial cells by Wnt/beta-catenin pathway and promote lung repair. However, whether fine particulate matter (PM2.5) could affect Wnt pathway and finally reduce the ability of MSCs to differentiate into epithelial cells is still unknown. This study aimed to investigate whether PM2.5 could inhibit the epithelial differentiation of human umbilical cord-derived MSCs cells (hUCMSCs) and the related underlying mechanism. hUCMSCs were incubated with different concentrations of PM2.5. Then, the cell viability, reactive oxygen species level, and single-cell sphere formation were assessed. The underlying mechanism of PM2.5 in epithelial differentiation of hUCMSCs was further evaluated by co-culturing hUCMSCs with A549 cells. Our results demonstrated that PM2.5 exposures could affect the expressions of beta-catenin and lung epithelial markers (zonula occludens-1 (ZO-1); cytokeratins 5 and 19) in the co-cultured hUCMSCs. The Wnt/beta-catenin pathway is involved in regulating the epithelial differentiation of MSCs. As expected, co-treatment with Wnt3a, which is the activator of the Wnt pathway, attenuated the downregulation of lung epithelial markers (ZO-1; cytokeratins 5 and 19) and paracrine factors (keratinocyte growth factor and hepatocyte growth factor) caused by PM2.5. Altogether, these results demonstrated that PM2.5 could affect the epithelial differentiation of hUCMSCs via the Wnt/beta-catenin pathway. (C) 2019 Elsevier Ltd. All rights reserved.