Ceramide inhibits connective tissue growth factor expression by human retinal pigment epithelial cells

被引：6
|
作者：
Sonoda, Shozo [1 ]
Nagineni, Chandrasekharam N. [2 ]
Kitamura, Mizuki [1 ]
Spee, Christine [3 ,4 ]
Kannan, Ram [1 ]
Hinton, David R. [3 ,4 ]
机构：
[1] Doheny Eye Inst, Arnold & Mabel Beckman Macular Res Ctr, Los Angeles, CA 90033 USA
[2] NEI, Immunol Lab, Bethesda, MD 20892 USA
[3] USC, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USA
[4] USC, Keck Sch Med, Dept Pathol, Los Angeles, CA USA
来源：
CYTOKINE | 2014年 / 68卷 / 02期
关键词：
Retinal pigment epithelium; Ceramide; TGF-beta; CTGF; Retinal fibrosis; PATHOGENESIS;
D O I：
10.1016/j.cyto.2014.03.011
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Connective tissue growth factor (CTGF) is known to be involved in retinal fibrotic disorders. We used human retinal pigment epithelial cells (HRPE), which play critical roles in retinal fibrosis, to examine the expression of CTGF and its regulation by ceramide and TGF-beta. Real-time PCR analysis showed downregulation of CTGF mRNA by C-2 ceramide and upregulation by TGF-beta. C-2 ceramide also inhibited constitutive and TGF-beta-enhanced CTGF secretion by HRPE cells. Predominant secretion (>80% of total) of CTGF from the apical side was observed in highly polarized HRPE cells. Fumonosin, an inhibitor of ceramide synthesis, stimulated CTGF secretion while 4HPR, an activator of ceramide synthesis, downregulated CTGF secretion. Based on these results demonstrating ceramide regulation of CTGF secretion by HRPE, we suggest that ceramide may have therapeutic potential for the treatment of retinal fibrotic diseases by inhibiting CTGF production. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：137 / 140
页数：4
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