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

页码：137 / 140

页数：4

共 14 条

[1] Connective tissue growth factor: Context-dependent functions and mechanisms of regulation
Cicha, Iwona
Goppelt-Struebe, Margarete
[J]. BIOFACTORS, 2009, 35 (02) : 200 - 208
[2] HANNUN YA, 1994, J BIOL CHEM, V269, P3125
[3] Identification of paracrine neuroprotective candidate proteins by a functional assay-driven proteomics approach
Hauck, Stefanie M.
Gloeckner, Christian J.
Harley, Margaret E.
Schoeffmann, Stephanie
Boldt, Karsten
Ekstrom, Per A. R.
Ueffing, Marius
[J]. MOLECULAR & CELLULAR PROTEOMICS, 2008, 7 (07) : 1349 - 1361
[4] A role for connective tissue growth factor in the pathogenesis of choroidal neovascularization
He, S
Jin, ML
Worpel, V
Hinton, DR
[J]. ARCHIVES OF OPHTHALMOLOGY, 2003, 121 (09) : 1283 - 1288
[5] Connective tissue growth factor as a mediator of intraocular fibrosis
He, Shikun
Chen, Youxin
Khankan, Rima
Barron, Ernesto
Burton, Richard
Zhu, DanHong
Ryan, Stephen J.
Oliver, Noelynn
Hinton, David R.
[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2008, 49 (09) : 4078 - 4088
[6] Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy
Hinton, DR
He, S
Jin, ML
Barron, E
Ryan, SJ
[J]. EYE, 2002, 16 (04) : 422 - 428
[7] MMP-2 and MMP-9 secretion by RPE is stimulated by angiogenic molecules found in choroidal neovascular membranes
Hoffmann, Stephan
He, Shikun
Ehren, Marianne
Ryan, Stephen J.
Wiedemann, Peter
Hinton, David R.
[J]. RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES, 2006, 26 (04): : 454 - 461
[8] Ceramide-induced apoptosis: Role of catalase and hepatocyte growth factor
Kannan, R
Jin, ML
Gamulescu, MA
Hinton, DR
[J]. FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (02) : 166 - 175
[9] Association of connective tissue growth factor with fibrosis in vitreoretinal disorders in the human eye
Kuiper, Esther J.
de Smet, Marc D.
van Meurs, Jan C.
Tan, H. Stevie
Tanck, Michael W. T.
Oliver, Noelynn
van Nieuwenhoven, Frans A.
Goldschmeding, Roel
Schlingemann, Reinier O.
[J]. ARCHIVES OF OPHTHALMOLOGY, 2006, 124 (10) : 1457 - 1462
[10] Intracellular signal transduction pathways activated by ceramide and its metabolites
Ruvolo, PP
[J]. PHARMACOLOGICAL RESEARCH, 2003, 47 (05) : 383 - 392

← 1 2 →