All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta
All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta
复制标题
全反式视黄酸通过视黄酸受体β调节人巩膜成纤维细胞中丝裂原激活蛋白激酶途径的激活
作者：
Xiao Yang;Zhenya Gao;Klaus Trier;Junwen Zeng
目的 全反式维甲酸（ATRA）已知可抑制人巩膜成纤维细胞（HSFs）的增殖并调节巩膜细胞间基质成分，因此可能作为一种控制眼球生长的介质。细胞增殖
Purpose All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed activation of the MAPK pathway could be involved in the response of HSFs exposed to ATRA. Methods HSFs were cultured in Dulbecco Modified Eagle's Medium/F12 (DMEM/F12) and exposed to 1 μmol/l ATRA for 10 min, 30 min, 1 h, 8 h, or 24 h. The activation of extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun N-terminal kinase (JNK) in HSFs was assessed with western blot analysis and immunocytofluorescence. Results After exposure to ATRA for 24 h, the HSFs appeared shrunken and thinner than the control cells. The intercellular spaces were wider, and the HSFs appeared less numerous than in the control culture. Western blot showed decreased activation of ERK 1/2 in the HSFs from 30 min (p=0.01) to 24 h (p<0.01) after the start of exposure to ATRA, and increased activation of the JNK protein from 10 to 30 min (p<0.01) after the start of exposure to ATRA. Indirect immunofluorescence confirmed changes in activation of ERK 1/2 and JNK in HSFs exposed to ATRA. No change in activation of p38 in HSFs was observed after exposure to ATRA. Pretreatment of the HSFs with LE135, an antagonist of retinoic acid receptor beta (RARβ), abolished the ATRA-induced changes inactivation of ERK 1/2 and JNK. Conclusions ATRA inhibits HSF proliferation by a mechanism associated with modulation of ERK 1/2 and JNK activation and depends on stimulation of retinoic acid receptor beta.
登录
查看更多内容
DOI：
10.3760/j.issn:0412-4081.2007.08.017
发表时间：
2007-08
期刊：
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology
影响因子：
--
作者：
D. Yan;Xiangtian Zhou;Xiao-yan Chen;F. Lü;Jiao Wang;D.-N. Hu;J. Qu
通讯作者：
D. Yan;Xiangtian Zhou;Xiao-yan Chen;F. Lü;Jiao Wang;D.-N. Hu;J. Qu
影响因子：
3.3
作者：
Zanobia A Syed;S. Cheepala;Jennifer N Gill;J. Stein;C. Nathan;J. DiGiovanni;V. Batra;P. Adegboyega;H. Kleiner;J. Clifford
通讯作者：
Zanobia A Syed;S. Cheepala;Jennifer N Gill;J. Stein;C. Nathan;J. DiGiovanni;V. Batra;P. Adegboyega;H. Kleiner;J. Clifford
影响因子：
8
作者：
F. Pettersson;Marie-Claude Couture;N. Hanna;W. Miller
通讯作者：
F. Pettersson;Marie-Claude Couture;N. Hanna;W. Miller
影响因子：
4.8
作者：
Li, Y;Hashimoto, Y;Zhang, XK
通讯作者：
Zhang, XK
影响因子：
3.4
作者：
Mertz, JR;Wallman, J
通讯作者：
Wallman, J