Notch 2 from bone marrow mesenchymal stem cells alleviates smoke inhalation-induced lung injury by mediating alveolar...

Smoke inhalation-induced lung injury (SILI) is the major fatality in fire- and blast-related accidents. Bone marrow mesenchymal stem cells (BMSCs) have a potential therapeutic role in SILI through directional differentiation into AT1, AT2, and pulmonary vascular endothelial cells. The present study proposes to evaluate the effect of Notch 2 on the directional differentiation of BMSCs and to characterize its reparative role in a SILI model.

pGMLV-SC5 RNAi and pcDNA 3.1 lentivirus exogenously regulate Notch 2 expression in rat-derived BMSCs and BMSCs were injected into the tail vein of the SILI rat model. H&E, Masson and TUNEL stains characterized pathological changes in rat lung tissue. ELISA, western blot, and RT-qPCR identified inflammatory factors (IL-1β, IL-6 and TNF-α), Notch 2 pathway- (Notch 2 and Hes1), lung fibrosis- (α-SMA and E-cadherin), AT1- (AQP5), and AT2- (SPC and SPD) associated markers.

pGMLV-SC5 RNAi or pcDNA 3.1 lentivirus could decrease or increase Notch 2 expression in BMSCs. In vivo imaging showed that BMSCs could be localized in the lungs of the SILI model at 24 h after model development. Treatment with BMSCs alleviated diffuse congestion, lung fibrosis, and alveolar cell apoptosis in lung tissues of the SILI model. Treatment of BMSCs decreased the levels of IL-1β, IL-6, TNF-α, and α-SMA and increased the expression of Notch 2, Hes1, E-cadherin, AQP5, SPC, and SPD in the SILI model. Overexpression of Notch 2 enhances the therapeutic effect of BMSCs on lung injury in the SILI model. Notably, overexpression of Notch 2 attenuated the BMSCs-induced upregulation of AQP5 expression and enhanced the BMSCs-induced upregulation of SPC and SPD expression.

Notch 2 contributes to lung injury repair in the SILI rat model by facilitating the differentiation of BMSCs to AT2. This study provides a new idea and target for the treatment of BMSCs for SILI.