Ye Xiaofeng, Xu Gezhi, Chang Qing, Fan Jiaweng, Sun Zhongcui, Qin Yaowu, Jiang Alice C
EENT Hospital, Eye Institute, Fudan University, Shanghai, China.
Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5226-33. doi: 10.1167/iovs.09-4899. Epub 2010 May 5.
Vascular endothelial growth factor (VEGF) is one of the major factors promoting diabetic retinopathy (DR). A better understanding of the signaling pathway in VEGF regulation is of clinical importance to identify more precise therapeutic targets for diabetic retinopathy. The ERK1/2 signaling pathway has been shown to play a key role in some oncoma and hematologic diseases by mediating VEGF release. This research was conducted to determine whether the ERK1/2 signaling pathway also plays a major role in VEGF release in DR development.
One hundred Sprague-Dawley (SD) rats were induced to diabetes by streptozotocin (STZ) injection and monitored at several time points (1, 2, 3, 4, 8, and 12 weeks) for ERK1/2 phosphorylation, Activator protein (AP)-1 activity and concentration, and VEGF protein and mRNA expression, using immunohistochemical and biochemical methods. RESULTS. The ERK1/2 signaling pathway was rapidly activated 1 week after diabetes was induced. AP-1, the downstream transcription factor of ERK1/2, was also activated, and VEGF became highly regulated in a similar trend. U0126, an inhibitor of ERK1/2, also downregulated VEGF expression, in addition to ERK1/2 and AP-1 activity.
ERK1/2 signaling pathway is involved in VEGF release in diabetic rat retina; therefore, ERK1/2 may be a potential therapeutic target of DR.
血管内皮生长因子（VEGF）是促进糖尿病视网膜病变（DR）的主要因素之一。更好地了解VEGF调节中的信号通路对于确定糖尿病视网膜病变更精确的治疗靶点具有临床重要性。ERK1/2信号通路已被证明通过介导VEGF释放，在一些肿瘤和血液疾病中起关键作用。本研究旨在确定ERK1/2信号通路在DR发展过程中VEGF释放是否也起主要作用。
通过注射链脲佐菌素（STZ）诱导100只Sprague-Dawley（SD）大鼠患糖尿病，并在几个时间点（1、2、3、4、8和12周）使用免疫组化和生化方法监测ERK1/2磷酸化、激活蛋白（AP）-1活性和浓度以及VEGF蛋白和mRNA表达。结果：糖尿病诱导后1周，ERK1/2信号通路迅速被激活。ERK1/2的下游转录因子AP-1也被激活，VEGF也以类似趋势受到高度调节。ERK1/2抑制剂U0126除了下调ERK1/2和AP-1活性外，还下调VEGF表达。
ERK1/2信号通路参与糖尿病大鼠视网膜中VEGF的释放；因此，ERK1/2可能是DR的潜在治疗靶点。
