TXNIP将先天宿主防御机制与慢性高血糖下视网膜Muller胶质细胞的氧化应激和炎症联系起来:对糖尿病视网膜病变的影响。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-03-18 DOI:10.1155/2012/438238
Takhellambam S Devi, Icksoo Lee, Maik Hüttemann, Ashok Kumar, Kwaku D Nantwi, Lalit P Singh
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引用次数: 181

摘要

硫氧还蛋白相互作用蛋白(TXNIP)介导实验性糖尿病视网膜炎症、胶质瘤和细胞凋亡。在这里,我们利用培养的大鼠Muller细胞系(rMC1)研究Muller胶质细胞对高糖(HG)和TXNIP表达的时间反应。我们研究了hg诱导的TXNIP表达是否在rMC1中引起宿主防御机制,以应对代谢异常。HG引起TXNIP持续上调(2小时至5天)、ROS生成、ATP消耗、内质网应激和炎症。HG可激活多种细胞防御机制:(i) NLRP3炎性体,(ii)内质网应激反应(sXBP1), (iii)缺氧样HIF-1α诱导,(iv)自噬/有丝自噬,(v)细胞凋亡。我们在体内也发现链脲佐菌素诱导的糖尿病大鼠视网膜TXNIP和先天免疫反应基因表达高于正常大鼠。通过玻璃体内siRNA敲低TXNIP可减少糖尿病视网膜的炎症(IL-1β)和胶质细胞增生(GFAP)。体外TXNIP消融可抑制ROS生成,恢复rMC1的ATP水平和自噬LC3B诱导。因此,我们的研究结果表明,HG维持Muller神经胶质中TXNIP的上调,并引发细胞防御/生存机制程序,最终导致氧化应激、内质网应激/炎症、自噬和凋亡。TXNIP是改善糖尿病视网膜病变致盲性眼部并发症的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy.

TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy.

TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy.

TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy.

Thioredoxin Interacting Protein (TXNIP) mediates retinal inflammation, gliosis, and apoptosis in experimental diabetes. Here, we investigate the temporal response of Muller glia to high glucose (HG) and TXNIP expression using a rat Muller cell line (rMC1) in culture. We examined if HG-induced TXNIP expression evokes host defense mechanisms in rMC1 in response to metabolic abnormalities. HG causes sustained up-regulation of TXNIP (2 h to 5 days), ROS generation, ATP depletion, ER stress, and inflammation. Various cellular defense mechanisms are activated by HG: (i) NLRP3 inflammasome, (ii) ER stress response (sXBP1), (iii) hypoxic-like HIF-1α induction, (iv) autophagy/mitophagy, and (v) apoptosis. We also found in vivo that streptozocin-induced diabetic rats have higher retinal TXNIP and innate immune response gene expression than normal rats. Knock down of TXNIP by intravitreal siRNA reduces inflammation (IL-1β) and gliosis (GFAP) in the diabetic retina. TXNIP ablation in vitro prevents ROS generation, restores ATP level and autophagic LC3B induction in rMC1. Thus, our results show that HG sustains TXNIP up-regulation in Muller glia and evokes a program of cellular defense/survival mechanisms that ultimately lead to oxidative stress, ER stress/inflammation, autophagy and apoptosis. TXNIP is a potential target to ameliorate blinding ocular complications of diabetic retinopathy.

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来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
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