Cellular mechanisms of high mobility group 1 (HMGB-1) protein action in the diabetic retinopathy.
Cellular mechanisms of high mobility group 1 (HMGB-1) protein action in the diabetic retinopathy.
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DOI：
10.1371/journal.pone.0087574
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ivanov D
中科院分区：
文献类型：
--
作者：
Santos AR;Dvoriantchikova G;Li Y;Mohammad G;Abu El-Asrar AM;Wen R;Ivanov D
糖尿病视网膜病变是糖尿病的主要微血管并发症之一，并且仍然是全世界失明的主要原因之一。最近的研究揭示了炎症和促血管生成高迁移率族 1 (HMGB-1) 细胞因子在糖尿病视网膜病变中的重要作用。为了阐明视网膜中 HMGB-1 活性的细胞机制，我们进行了这项研究。糖尿病视网膜病变的组织学特征包括血管周细胞和内皮细胞的损失，以及异常的新血管生长。为了确定 HMGB-1 在内皮细胞和周细胞脆弱性中的作用，用 HMGB-1 处理这些细胞的培养物或与神经胶质细胞的共培养物，并评估 24 小时后的存活率。通过定量RT-PCR检测神经胶质细胞和内皮细胞中细胞因子、趋化因子和细胞粘附分子的表达水平，以评估HMGB-1处理后这些细胞的变化。新生血管形成的动物模型也被用来研究 HMGB-1 在视网膜中的作用。我们报道周细胞死亡是由 HMGB-1 诱导的胶质细胞细胞毒活性介导的，而 HMGB-1 可以直接介导内皮细胞的死亡。我们还发现 HMGB-1 影响内皮细胞活性。然而，与对照眼相比，我们没有观察到 HMGB-1 处理的眼睛之间的新血管形成水平存在差异，也没有观察到用 HMGB-1 处理的神经胶质细胞和对照细胞之间的促血管生成细胞因子 VEGF-A 表达水平存在差异。我们的数据还表明，HMGB-1 不参与氧诱导视网膜病变模型中的视网膜新生血管形成。因此，我们的数据表明，糖尿病视网膜病变中视网膜周细胞和内皮损伤和死亡可能是由于HMGB-1诱导的神经胶质细胞的细胞毒活性以及HMGB-1对内皮细胞的直接作用所致。同时，我们的研究结果表明HMGB-1在视网膜和脉络膜新生血管形成中起不显着的作用。
Diabetic retinopathy is one of the main microvascular complications of diabetes and remains one of the leading causes of blindness worldwide. Recent studies have revealed an important role of inflammatory and proangiogenic high mobility group 1 (HMGB-1) cytokine in diabetic retinopathy. To elucidate cellular mechanisms of HMGB-1 activity in the retina, we performed this study. The histological features of diabetic retinopathy include loss of blood-vessel pericytes and endothelial cells, as well as abnormal new blood vessel growth. To establish the role of HMGB-1 in vulnerability of endothelial cells and pericytes, cultures of these cells, or co-cultures with glial cells, were treated with HMGB-1 and assessed for survival after 24 hours. The expression levels of the cytokines, chemokines, and cell adhesion molecules in glial and endothelial cells were tested by quantitative RT-PCR to evaluate changes in these cells after HMGB-1 treatment. Animal models of neovascularization were also used to study the role of HMGB-1 in the retina. We report that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate death of endothelial cells. We also found that HMGB-1 affects endothelial cell activity. However, we did not observe a difference in the levels of neovascularization between HMGB-1-treated eyes compared to the control eyes, nor in the levels of proangiogenic cytokine VEGF-A expression between glial cells treated with HMGB-1 and control cells. Our data also indicate that HMGB-1 is not involved in retinal neovascularization in the oxygen-induced retinopathy model. Thus, our data suggest that retinal pericyte and endothelial injury and death in diabetic retinopathy may be due to HMGB-1-induced cytotoxic activity of glial cells as well as the direct effect of HMGB-1 on endothelial cells. At the same time, our findings indicate that HMGB-1 plays an insignificant role in retinal and choroidal neovascularization.
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