All-trans retinoic acid upregulates the expression of ciliary neurotrophic factor in retinal pigment epithelial cells
All-trans retinoic acid upregulates the expression of ciliary neurotrophic factor in retinal pigment epithelial cells
复制标题
全反式视黄酸上调视网膜色素上皮细胞中睫状神经营养因子的表达
DOI：
10.1002/cbf.3264
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发表时间：
2017-06-01
影响因子：
3.6
通讯作者：
Zhou, Guo-Ping
中科院分区：
文献类型：
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作者：
Zhou, Wen-Di;Wang, Lu-Lu;Zhou, Guo-Ping
早产儿视网膜病变是低出生体重儿视力损害的主要原因，仍然是一个关键的治疗挑战。睫状神经营养因子（CNTF）是一种前髓鞘形成营养因子，可促进视杆细胞和视锥细胞的存活，并促进退化视网膜中视锥细胞外节的再生。睫状神经营养因子的表达受全反式维甲酸（ATRA）等多种因素的调节。在本研究中，我们发现ATRA以剂量和时间依赖的方式增加小鼠视网膜色素上皮（RPE）细胞中CNTF的表达，PKA信号通路是ATRA诱导CNTF上调所必需的。此外，我们发现，全反式维甲酸促进CNTF的表达，通过CREB结合到其启动子区。另外，早产儿视网膜病变血清和氧诱导视网膜病变小鼠视网膜组织中的CNTF水平降低。高氧培养的RPE细胞CNTF表达和分泌减少，ATRA处理后可恢复。总之，我们的数据表明，全反式维甲酸管理上调睫状神经营养因子在RPE细胞的表达。
Retinopathy of prematurity, a leading cause of visual impairment in low birth-weight infants, remains a crucial therapeutic challenge. Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor that promotes rod and cone photoreceptor survival and cone outer segment regeneration in the degenerating retina. Ciliary neurotrophic factor expression is regulated by many factors such as all-trans retinoic acid (ATRA). In this study, we found that ATRA increased CNTF expression in mouse retinal pigment epithelial (RPE) cells in a dose- and time-dependent manner, and PKA signaling pathway is necessary for ATRA-induced CNTF upregulation. Furthermore, we showed that ATRA promoted CNTF expression through CREB binding to its promoter region. In addition, CNTF levels were decreased in serum of retinopathy of prematurity children and in retinal tissue of oxygen-induced retinopathy mice. In mouse RPE cells cultured with high oxygen, CNTF expression and secretion were decreased, but could be recovered after treatment with ATRA. In conclusion, our data suggest that ATRA administration upregulates CNTF expression in RPE cells.