Protective effect of COMP-angiopoietin-1 on peritoneal vascular permeability and peritoneal transport function in uremic peritoneal dialysis rats

被引:1
作者
Shi, Yuanyuan [1 ,2 ,3 ]
Xiong, Yifan [1 ]
Lei, Yutian [1 ]
Li, Zhenyuan [1 ]
Yan, Hao [1 ]
Yuan, Jiangzi [1 ]
Ding, Feng [2 ,3 ]
Fang, Wei [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Nephrol, 1630 Dongfang Rd, Shanghai 200127, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Div Nephrol, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Unit Crit Nephrol, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China
来源
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH | 2019年 / 11卷 / 09期
基金
中国国家自然科学基金;
关键词
Peritoneal dialysis; COMP angiopoietin 1; vascular permeability; peritoneal transport function; DESIGNED ANGIOPOIETIN-1 VARIANT; VE-CADHERIN; ADHERENS JUNCTIONS; TECHNIQUE FAILURE; CELL JUNCTIONS; MECHANISMS; PERICYTES; MICE; PATHOPHYSIOLOGY; INTERNALIZATION;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The angiopoietin-1 (Ang-1)/Tie-2 signaling pathway plays a crucial role in the maintenance of vascular stabilization and permeability. In this study, we evaluated the protective effect of a designed Ang-1 variant (COMP-Ang-1) on peritoneal vascular permeability and peritoneal transport function in a uremic peritoneal dialysis (PD) model. Compared to the sham controls, uremic rats were characterized by decreased pericyte coverage and down-regulated endothelial junction expression. The permeability of the peritoneal vasculature to FITC-BSA and FITC-dextran in uremic rats was also higher than that in the sham controls, as well as increased levels of proinflammatory adhesion molecules and cytokines, increased D/P-cr and decreased ultrafiltration. Such changes were more marked in uremia+PD rats after exposure to glucose based peritoneal dialysis fluid (PDF) for 4 weeks. Peritoneal Ang-1 protein expression and Tie-2 phosphorylation were significantly lower in uremic rats than in control rats and were further significantly reduced in uremia+PD rats. After COMP-Ang-1 administration, phosphorylation of the Tie-2 receptor was significantly increased. Treatment with COMP-Ang-1 also significantly enhanced pericyte coverage, upregulated endothelial junction protein expression and inhibited leakage of FITC-BSA and FITC-dextran from the peritoneal vasculature induced during PD therapy; these changes were accompanied by reduced peritoneal tissue levels of proinflammatory adhesion molecules and cytokines, decreased D/P-cr and increased ultrafiltration. These findings suggest that COMP-Ang-1 may exert a protective effect against glucose based PDF-induced peritoneal vascular permeability and inflammation, at least in part, by enhancing pericyte coverage and endothelial junction protein expression, which subsequently significantly improves peritoneal transport function.
引用
收藏
页码:5932 / 5943
页数:12
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