The involvement of high mobility group 1 cytokine and phospholipases A2 in diabetic retinopathy.
The involvement of high mobility group 1 cytokine and phospholipases A2 in diabetic retinopathy.
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DOI：
10.1186/1476-511x-13-156
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发表时间：
2014-10-08
影响因子：
4.5
通讯作者：
Li ZH
中科院分区：
文献类型：
--
作者：
Gong Y;Jin X;Wang QS;Wei SH;Hou BK;Li HY;Zhang MN;Li ZH
糖尿病视网膜病变是糖尿病的主要微血管并发症，也是世界范围内致盲的主要原因之一。炎症/促血管生成高迁移率族1(HMGB-1)细胞因子和磷脂酶A2(PLA2)在新生血管中的作用的有趣报道转移了我们的注意力，以揭示HMGB-1和PLA2是否在糖尿病视网膜病变中发挥作用。我们在链脲佐菌素(STZ)诱导的糖尿病大鼠模型上进行了研究。用定量RT-PCR方法检测视网膜组织中细胞因子、趋化因子和细胞黏附分子的表达水平。检测HMGB-1、PLA2蛋白水平及血管内皮生长因子、肿瘤坏死因子-α、白介素1β和细胞间黏附分子-1水平。观察视网膜周细胞、内皮细胞损伤/死亡和血-视网膜屏障(BRB)的破坏情况。糖尿病大鼠视网膜微血管中HMGB-1、PLA2和IL-1β的蛋白表达显著增加。糖尿病大鼠视网膜血管内皮生长因子、细胞间黏附分子-1和肿瘤坏死因子-α水平也较高。进一步的研究发现，周细胞的死亡是由HMGB-1诱导的神经胶质细胞的细胞毒作用所介导的，而HMGB-1可以直接介导内皮细胞的死亡。类似地，PLA2的表达增加代表了糖尿病介导的BRB的改变，可能是上调了VEGF的表达。我们的数据提示HMGB-1和PLA2参与了糖尿病视网膜病变中视网膜周细胞和内皮细胞的损伤和细胞死亡。从这项研究中，我们认为HMGB-1和PLA2可能是治疗糖尿病视网膜病变的有趣靶点。
Diabetic retinopathy, the main microvascular complications of diabetes and one of the leading causes of blindness worldwide. Interesting reports on the role of inflammatory/proangiogenic high mobility group 1 (HMGB-1) cytokine and phospholipases A2 (PLA2) in neovascularization have diverted our concentration to reveal whether HMGB-1 and PLA2 plays role in diabetic retinopathy. We performed our study in streptozotocin (STZ)-induced diabetic rat model. The expression levels of the cytokines, chemokines, and cell adhesion molecules in retinal tissues were evaluated by quantitative RT-PCR. HMGB-1 and PLA2 protein levels along with VEGF, TNF-α, IL-1β and ICAM-1 levels were also measured. We observed the retinal pericytes, endothelial injury/death and breakdown of blood–retinal barrier (BRB). The protein expression of HMGB-1, PLA2 and IL-1β were significantly increased in micro vessels from retina of diabetic rats. Diabetic rats had also high retinal levels of VEGF, ICAM-1 and TNF-α. Further investigation revealed that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate endothelial cell death. Similarly, increased expression of PLA2 represents the diabetic mediated alteration of BRB, perhaps up regulating the VEGF. Our data suggest that HMGB-1 and PLA2 involved in retinal pericyte and endothelial injury and cell death in diabetic retinopathy. From this study, we suggest that HMGB-1 and PLA2 may be interesting targets in managing diabetic retinopathy.