Soluble Tie2 fusion protein decreases peritoneal angiogenesis in uremic rats

Xiao,Jing; Guo,Jia; Liu,Xin-Xin; Zhang,Xiao-Xue; Li,Zhen‑Zhen; Zhao,Zhan-Zheng; Liu,Zhang-Suo

doi:10.3892/mmr.2013.1478

Soluble Tie2 fusion protein decreases peritoneal angiogenesis in uremic rats

Authors:
- Jing Xiao
- Jia Guo
- Xin-Xin Liu
- Xiao-Xue Zhang
- Zhen‑Zhen Li
- Zhan-Zheng Zhao
- Zhang-Suo Liu
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Affiliations: Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Key Disciplines Laboratory Clinical Medicine Henan, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: May 16, 2013 https://doi.org/10.3892/mmr.2013.1478
Pages: 267-271

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Abstract

Angiogenesis is considered to be one of the most common mechanisms leading to ultrafiltration failure (UFF) in long-term peritoneal dialysis (PD) patients. The angiopoietin (Ang)/Tie system was found to play a role in the initiation of pathological neoangiogenesis and is also involved in peritoneal angiogenesis caused by peritoneal fluid. This aim of this study was to investigate the effects of the soluble Tie2 fusion protein (sTie2/Fc) on peritoneal angiogenesis in PD-treated uremic rats. The rats were divided into 6 groups: normal, sham surgery, uremic rats without PD, uremic PD-treated rats, uremic rats treated with PD and sTie2/Fc (0.25 µg/100 g) and uremic rats treated with PD and sTie2/Fc (0.5 µg/100 g). PD rats were treated once a day for 28 days prior to testing. Real-time polymerase chain reaction (RT-PCR) or tissue immunohistochemical staining was used to detect Ang-2 mRNA or protein expression in the peritoneal tissues of each group. The microvessel density (MVD) of the peritoneum was detected and quantified by immunohistochemical staining using the anti-CD34 antibody. Compared with the control group, Ang-2 mRNA and protein expression was significantly upregulated in the uremic and PD groups (P<0.05). MVD in the experimental group increased compared with the control group. sTie2/Fc treatment decreased the levels of Ang-2 mRNA and protein expression (P<0.05) in a dose-dependent manner and decreased PD-induced MVD in the peritoneum. In conclusion, angiogenesis of the peritoneum induced by PD was inhibited using sTie2/Fc in a uremic rat model.

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1	van Westrhenen R, Zweers MM, Kunne C, de Waart DR, van der Wal AC and Krediet RT: A pyruvate-buffered dialysis fluid induces less peritoneal angiogenesis and fibrosis than a conventional solution. Perit Dial Int. 28:487–496. 2008.PubMed/NCBI
2	Saxena R: Pathogenesis and treatment of peritoneal membrane failure. Pediatr Nephrol. 23:695–703. 2008. View Article : Google Scholar : PubMed/NCBI
3	Ramsauer M and D’Amore PA: Getting Tie(2)d up in angiogenesis. J Clin Invest. 110:1615–1617. 2002. View Article : Google Scholar : PubMed/NCBI
4	Koh GY, Kim I, Kwak HJ, Yun MJ and Leem JC: Biomedical significance of endothelial cell specific growth factor, angiopoietin. Exp Mol Med. 34:1–11. 2002. View Article : Google Scholar : PubMed/NCBI
5	Guo P, Imanishi Y, Cackowski FC, et al: Up-regulation of angiopoietin-2, matrix metalloprotease-2, membrane type 1 metalloprotease, and laminin 5 gamma 2 correlates with the invasiveness of human glioma. Am J Pathol. 166:877–890. 2005. View Article : Google Scholar : PubMed/NCBI
6	Reiss Y: Angiopoietins. Recent Results Cancer Res. 180:3–13. 2010. View Article : Google Scholar : PubMed/NCBI
7	Shin HY, Kim JH, Phi JH, et al: Endogenous neurogenesis and neovascularization in the neocortex of the rat after focal cerebral ischemia. J Neurosci Res. 86:356–367. 2008. View Article : Google Scholar : PubMed/NCBI
8	Mandriota SJ and Pepper MS: Regulation of angiopoietin-2 mRNA levels in bovine microvascular endothelial cells by cytokines and hypoxia. Circ Res. 83:852–859. 1998. View Article : Google Scholar : PubMed/NCBI
9	Yuan J, Fang W, Lin A, Ni Z and Qian J: Angiopoietin-2/Tie2 signaling involved in TNF-α induced peritoneal angiogenesis. Int J Artif Organs. 35:655–662. 2012.PubMed/NCBI
10	Yuan J, Fang W, Ni Z, et al: Peritoneal morphologic changes in a peritoneal dialysis rat model correlate with angiopoietin/Tie-2. Pediatr Nephrol. 24:163–170. 2009. View Article : Google Scholar : PubMed/NCBI
11	Lin P, Polverini P, Dewhirst M, Shan S, Rao PS and Peters K: Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. J Clin Invest. 100:2072–2078. 1997. View Article : Google Scholar : PubMed/NCBI
12	Zhao ZZ, Cao Y, Liu ZS, et al: Effects of recombinant human endostatin on peritoneal angiogenesis in peritoneal dialysis rats. Nephrology (Carlton). 16:599–606. 2011. View Article : Google Scholar : PubMed/NCBI
13	Gao D, Zhao ZZ, Liang XH, Li Y, Cao Y and Liu ZS: Effect of peritoneal dialysis on expression of vascular endothelial growth factor, basic fibroblast growth factor and endostatin of the peritoneum in peritoneal dialysis patients. Nephrology (Carlton). 16:736–742. 2011. View Article : Google Scholar
14	Ghosh SS, Krieg RJ, Sica DA, Wang R, Fakhry I and Gehr T: Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system. Pediatr Nephrol. 24:367–377. 2009. View Article : Google Scholar : PubMed/NCBI
15	Zhang XD and Qian JQ: An improved animal model of peritoneal dialysis mimicked human peritoneal dialysis. Chin J Blood Purif. 4:326–328. 2005.
16	Bunone G, Vigneri P, Mariani L, et al: Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features. Am J Pathol. 155:1967–1976. 1999. View Article : Google Scholar : PubMed/NCBI
17	Deng MY, Wang H, Ward GB, Beckham TR and McKenna TS: Comparison of six RNA extraction methods for the detection of classical swine fever virus by real-time and conventional reverse transcription-PCR. J Vet Diagn Invest. 17:574–578. 2005. View Article : Google Scholar : PubMed/NCBI
18	Sambrook J and Russell DW: Molecular Cloning: A Laboratory Manual. 3rd edition. CSHL Press; Cold Spring Harbor, NY: 2001
19	Weidner N: Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol. 147:9–19. 1995.PubMed/NCBI
20	Chaudhary K: Peritoneal dialysis drop-out: causes and prevention strategies. Int J Nephrol. 2011:4346082011. View Article : Google Scholar : PubMed/NCBI
21	Noh H, Kim JS, Han KH, et al: Oxidative stress during peritoneal dialysis: implications in functional and structural changes in the membrane. Kidney Int. 69:2022–2028. 2006. View Article : Google Scholar : PubMed/NCBI
22	Parikova A, Smit W, Struijk DG and Krediet RT: Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure. Kidney Int. 70:1988–1994. 2006.PubMed/NCBI
23	Margetts PJ, Gyorffy S, Kolb M, et al: Antiangiogenic and antifibrotic gene therapy in a chronic infusion model of peritoneal dialysis in rats. J Am Soc Nephrol. 13:721–728. 2002.PubMed/NCBI
24	Hanahan D and Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:353–364. 1996. View Article : Google Scholar : PubMed/NCBI
25	Zhao ZZ, Liu ZS and Liang XH: Expression and significance of aquaporin and basic fibroblast growth factor in human peritoneal mesothelial cells. Chin J Nephrol. 24:669–670. 2008.
26	Zhao ZZ, Cao Y and Liu ZS: The effects of recombinant human edostatin on peritoneul angiogenesis in peritoneal dialysis rats. Chin J Nephrol. 29:791–795. 2010.
27	Donnelly R and Yeung JM: Therapeutic angiogenesis: a step forward in intermittent claudication. Lancet. 359:2048–2050. 2002. View Article : Google Scholar : PubMed/NCBI
28	Takagi H, Koyama S, Seike H, et al: Potential role of the angiopoietin/tie2 system in ischemia-induced retinal neovascularization. Invest Ophthalmol Vis Sci. 44:393–402. 2003. View Article : Google Scholar : PubMed/NCBI
29	Zhang H and Liu ZL: Suppression of experimental choroidal neovascularization by soluble Tie2 fusion protein. Int J Ophthalmol. 8:272–274. 2008.
30	Shibuya M: Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis. BMB Rep. 41:278–286. 2008. View Article : Google Scholar : PubMed/NCBI
31	Selgas R, del Peso G, Bajo MA, et al: Vascular endothelial growth factor (VEGF) levels in peritoneal dialysis effluent. J Nephrol. 14:270–274. 2001.PubMed/NCBI