Potential Role Of The Jagged1/Notch1 Signaling Pathway In The Endothelial-Myofibroblast Transition During Blm-Induced Pulmonary Fibrosis

Endothelial cell myofibroblast transition (EndoMT) is found during the process of bleomycin (BLM)-induced pulmonary fibrosis in rats, and plays a very important role in sustaining inflammation and collagen secretion. Moreover, some studies have suggested that the Notch1 signaling pathway may be involved in the expression of a-smooth muscle actin (alpha-SMA) in pulmonary microvascular endothelial cells (PMVECs), a protein marker of EndoMT. Therefore, we aimed to investigate the expression level of alpha-SMA and Notch1-related signaling molecules in PMVECs from BLM-induced rats and determine the relationship between the Notch1 signaling pathway and the expression of alpha-SMA in PMVECs. We found that the expression levels of alpha-SMA, Notch1, and Jagged1 were upregulated, while the expression levels of Dll4 were downregulated. Furthermore, there was a positive correlation between the expression of Jagged1 and the a-SMA proteins in PMVECs, and NF-kappa B was downregulated by decreasing the expression of Jagged1. In conclusion, the Jagged1/Notch1 signaling pathway is activated in PMVECs during the pathogenesis of BLM-induced pulmonary fibrosis in rats, and it may induce alpha-SMA expression via a non-canonical pathway involving NF-kappa B as the target molecule. The precise mechanism and the molecules involved in this signaling pathway need to be further elucidated.