Notch activity is increased in a rat peritoneal fibrosis model induced by high glucose dialysate / 中华肾脏病杂志

ABSTRACT

Objective To investigate the role of Notch signaling in the progression of peritoneal fibrosis in a rat model induced by high glucose dialysate. Methods Male Sprague Dawley rats were subjected to daily peritoneal dialysis (PD) with a lactate-buffered solution containing 4.25% glucose. They were sacrificed at 2 and 4 weeks after PD. The parietal thickness was measured with Masson staining. The expression of TGF-β1, E-cadherin, α-SMA and collagen Ⅰ was examined by immunoblotting. The expression of Notch ligand Jagged-1 and the negative Notch signaling regulato--Numb was analyzed by both immunoblotting and RT-PCR. The expression of a Notch nuclear target gene Hcs-1 was examined by RT-PCR. Results Both HE and Masson trichrome staining revealed an increase in peritoneal thickness with a loss of mesothelial cells and a rich of collagen matrix deposition in the submesothelial zone was evident at 4 weeks after PD. Meanwhile, compared to healthy rats, the expression of TGF-β1, ct-SMA and collagen Ⅰ was significantly increased, but the expression of E-cadherin was decreased in peritoneum after PD treatment. It was difficult to detect the Jagged-1 and Hes-1 expression in normal peritoneum, but their expression was graduaUy increased after PD. In contrast, the expression level of Numb, a negative regulator of Notch signaling, was dramatically decreased after PD. Conclusions Notch signaling is activated during the process of PD-induced peritoneal fibrosis and the activation of Notch signaling is associated with the loss of negative regulation of Notch signaling via decreased expression of Numb. Inhibition of Notch signaling via overexpression of its negative regulators such as Numb may be a novel therapeutic approach for peritoneal fibrosis in PD patients.