Bone marrow mesenchymal stem cells protect lungs from smoke inhalation injury by differentiating into alveolar epithelial cells via Notch signaling

Abstract

To examine the protective effect of transplanting bone marrow mesenchymal stem cells (BMSCs) in treating lung injury induced by smoke exposure and to investigate the underlying mechanisms of this protection. SD rats were randomly divided into four groups: normal group, normal + BMSC^GFP group, smoke group, and smoke + BMSC^GFP group. To detect lung injury, we measured arterial blood gas, the wet-to-dry weight ratio, and levels of interleukin-1β, tumor necrosis factor-α, interleukin-10, and interleukin-13 in bronchoalveolar lavage fluid and lung tissues. We also conducted histopathology examinations. The protein markers of alveolar epithelial cells were measured to determine the BMSC differentiation. The protein levels of Notch1, Jagged-1, and Hes-1 also were detected. In the present study, BMSC transplantation significantly decreased the wet-dry weight ratio of the lung, reduced the production of inflammatory mediators, and alleviated lung injury simply through differentiating into alveolar type II cells and alveolar type I cells. Western blot analysis confirmed that the protein expression of Notch-1, Jagged-1, and Hes-1 increased significantly after systemic BMSC transplantation. No significant difference was observed between the normal group and the normal + BMSC^GFP group. Our findings indicate that systemic transplantation of BMSCs alleviated lung injury induced by smoke exposure, which may be associated with BMSCs’ ability to differentiate into alveolar-type cells via the Notch signaling pathway.