Simultaneous application of bevacizumab and anti-CTGF antibody effectively suppresses proangiogenic and profibrotic factors in human RPE cells.

Autor:	Bagheri A; National Institute of Genetic Engineering and Biotechnology, Tehran, Iran., Soheili ZS; National Institute of Genetic Engineering and Biotechnology, Tehran, Iran., Ahmadieh H; Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Samiei S; Blood Transfusion Research Center High Institute for Research and Education in Transfusion Medicine, Tehran, Iran., Sheibani N; Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI., Astaneh SD; National Institute of Genetic Engineering and Biotechnology, Tehran, Iran., Kanavi MR; Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Mohammadian A; National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Jazyk:	angličtina
Zdroj:	Molecular vision [Mol Vis] 2015 Apr 10; Vol. 21, pp. 378-90. Date of Electronic Publication: 2015 Apr 10 (Print Publication: 2015).
Abstrakt:	Purpose: Retinal pigment epithelial (RPE) cells play key roles in the development of choroidal neovascularization and subsequent fibrosis. We investigated the impact of bevacizumab, antihuman vascular endothelial growth factor (VEGF) antibody, and anticonnective tissue growth factor (anti-CTGF) neutralizing antibody, individually or in combination, on proangiogenic and profibrotic properties of RPE cells. Methods: Primary cultures of human RPE cells were incubated with different concentrations of bevacizumab (0.25, 0.5, and 0.8 mg/ml) and/or anti-CTGF (10 μg/ml), and cell proliferation and apoptosis were determined. Expression and activity of proangiogenic and profibrotic genes including matrix metalloproteinases (MMP)-2 and 9, VEGFA, CTGF, vascular endothelial growth factor receptor-1 (VEGFR-1), cathepsin D, tissue inhibitor of metalloproteinases (TIMP) -1 and -2, and alpha smooth muscle actin (α-SMA) were assessed with slot blot, real-time RT-PCR, and zymography. Results: Bevacizumab alone inhibited proliferation of RPE cells while anti-CTGF or bevacizumab and anti-CTGF combined had no inhibitory effect in this regard. Bevacizumab increased MMP-2, MMP-9, and cathepsin D but decreased VEGFA and VEGFR-1 expression. The CTGF level was increased by using 0.25 mg/ml bevacizumab but decreased at the 0.8 mg/ml concentration of bevacizumab. Treatment with anti-CTGF antibody decreased MMP-2 expression whereas combined treatment with bevacizumab and anti-CTGF resulted in decreased expression of MMP-2, TIMP-1, cathepsin D, VEGFA, CTGF, and α-SMA in the treated cultures. Conclusions: Treatment of RPE cells with the combination of bevacizumab and anti-CTGF could effectively suppress the proangiogenic and profibrotic activity of RPE cells.
Databáze:	MEDLINE
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