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Clinical and Experimental Nephrology
Published in: Clinical and Experimental Nephrology 2/2018

01-04-2018 | Original article

Pharmacological inhibition of heparin-binding EGF-like growth factor promotes peritoneal angiogenesis in a peritoneal dialysis rat model

Authors: Zhenyuan Li, Hao Yan, Jiangzi Yuan, Liou Cao, Aiwu Lin, Huili Dai, Zhaohui Ni, Jiaqi Qian, Wei Fang

Published in: Clinical and Experimental Nephrology | Issue 2/2018

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Abstract

Background

Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model.

Methods

32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group: subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD: uremic rats that were dialyzed with Dianeal® for 4 weeks; (4) CRM 197 group: dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot.

Results

Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p < 0.05). CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p < 0.001).

Conclusion

PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.
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Metadata
Title
Pharmacological inhibition of heparin-binding EGF-like growth factor promotes peritoneal angiogenesis in a peritoneal dialysis rat model
Authors
Zhenyuan Li
Hao Yan
Jiangzi Yuan
Liou Cao
Aiwu Lin
Huili Dai
Zhaohui Ni
Jiaqi Qian
Wei Fang
Publication date
01-04-2018
Publisher
Springer Singapore
Published in
Clinical and Experimental Nephrology / Issue 2/2018
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-017-1440-7

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