Nuclear Respiratory Factor-1 (NRF-1) Regulates Transcription of the CXC Receptor 4 (CXCR4) in the Rat Retina
Nuclear Respiratory Factor-1 (NRF-1) Regulates Transcription of the CXC Receptor 4 (CXCR4) in the Rat Retina
复制标题
核呼吸因子 1 (NRF-1) 调节大鼠视网膜中 CXC 受体 4 (CXCR4) 的转录
DOI:
10.1167/iovs.17-22115
复制
发表时间:
2017-09-01
影响因子:
4.4
通讯作者:
Zhuang, Jing
中科院分区:
文献类型:
--
作者:
Chen, Pei;Cai, Xiaoxiao;Zhuang, Jing
PURPOSE. The CXC receptor 4 (CXCR4)is required for various physiologic and pathologic processes in the eye, including stem cell trafficking, neuronal development, immune responses, and ocular neovascularization. Here, we used the rat retina models to determine the mechanisms driving CXCR4 transcription.METHODS. The expression pattern of CXCR4 and nuclear respiratory factor-1 (NRF-1) were profiled in the rat retina during the course of development. Chromatin immunoprecipitation (CHiP) assay determined the transcriptional mechanism of CXCR4 in rat retina. A rat model of oxygen-induced retinopathy (OIR) that mimics retinal ischemia-reperfusion injury was established. Under either normoxic or hypoxic conditions, CXCR4 and NRF-1 expression in rat retinas was tracked by RT-PCR and Western analysis. Immunofluorescence staining localized CXCR4 and NRF-1.RESULTS. Both CXCR4 and NRF-1 were highly expressed in the neonatal rat retina, downregulated in parallel, and silenced in fully developed retinas (1 month of age). ChIP assays revealed that NRF-1 was required for CXCR4 promoter activity in rat retinas. In the OIR rat model, retinal hypoxia induced up-regulation of CXCR4 and NRF-1 concurrently.CONCLUSIONS. Our findings suggest that NRF-1 regulates the expression of CXCR4 in normal retinal development and in pathologic processes of retinal hypoxia and neovascularization.