title: The expression levels of Notch-related signaling molecules in pulmonary microvascular endothelial cells in bleomycin-induced rat pulmonary fibrosis.
abstract: Previous studies have suggested that the Notch signaling pathway plays a very important role in the proliferation and differentiation of pulmonary microvascular endothelial cells (PMVECs). Therefore, we aimed to investigate the expression level of Notch-related signaling molecules in PMVECs in bleomycin (BLM)-induced rat pulmonary fibrosis. Immunohistochemistry, immunofluorescence, Western blotting, and real-time PCR were used to analyze the differences in protein and mRNA expression levels of Notch-related signaling molecules, i.e. Notch1, Jagged1, Delta-like ligand 4 (Dll4), and hairy and enhancer of split homolog 1 (Hes1), between a control group treated with intratracheal instillation of saline and a study group treated with intratracheal instillation of BLM solution. Expression levels of the receptor Notch1 and one of its ligands, Jagged1, were upregulated, while the expression levels of the ligand Dll4 and the target molecule of the Notch signaling pathway, Hes1, were downregulated. The differences in protein and mRNA expression levels between the control and study groups were significant (p<0.001). The Jagged1/Notch1 signaling pathway is activated in the pathogenesis of BLM-induced rat pulmonary fibrosis, while the Dll4/Notch1 signaling pathway is inhibited, which inhibits the suppressive effect of Dll4/Notch1 signaling on PMVEC overproliferation, further causing PMVEC dysfunction in cell sprouting and maturation as well as abnormal differentiation of the cell phenotype. Conversely, the down-expression of Hes1 indicates that the Jagged1/Notch1 signaling pathway could be a non-canonical Notch signaling pathway independent of Hes1 activation, which differs from the canonical Dll4/Notch1 signaling pathway.
authors.affiliation: Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xian, P. R. China cissia@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yin
authors.forename: Weihua
authors.initials: W
authors.lastname: Wang
authors.forename: Guangbin
authors.initials: G
authors.lastname: Cui
authors.forename: Haiyan
authors.initials: H
authors.lastname: Nan
authors.forename: Linfeng
authors.initials: L
authors.lastname: Yan
authors.forename: Wenhu
authors.initials: W
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Jingguo
authors.initials: J
authors.lastname: Wei
mesh_terms: D000818:Animals; D001761:Bleomycin; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D051880:Receptors, Notch / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch; D001761:Bleomycin