title: Notch Signaling Molecules Activate TGF- β in Rat Mesangial Cells under High Glucose Conditions.
abstract: The involvement of the Notch signaling pathway in the cellular differentiation of the mammalian kidney is established. Recently, the dysregulation of Notch signaling molecules has been identified in acute and chronic renal injuries, fibrosis models, and diabetic kidney biopsies. The canonical Notch ligand , Jagged1, is upregulated in a transforming growth factor-beta- (TGF- β -) dependent manner during chronic kidney disease. TGF- β , a central mediator of renal fibrosis, also is a major contributor to the development of diabetic nephropathy. To explore the roles and possible mechanisms of Notch signaling molecules in the pathogenesis of diabetic nephropathy, we exposed cultured rat mesangial cells to a γ -secretase inhibitor (DAPT) or high glucose and measured the expression of Notch signaling molecules and the fibrosis index. Notch pathway-related molecules, TGF- β , and fibronectin increased with exposure to high glucose and decreased with DAPT treatment. Our results suggest that the Notch signaling pathway may precipitate diabetic nephropathy via TGF- β activation.
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China ; Department of Endocrinology, The People's Hospital of Yongchuan, Yongchuan, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Chenlin
authors.initials: C
authors.lastname: Gao
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Wan
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu