Hyperglycemia induces Toll like receptor 4 expression and activity in mouse mesangial cells: relevance to diabetic nephropathy
Hyperglycemia induces Toll like receptor 4 expression and activity in mouse mesangial cells: relevance to diabetic nephropathy
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DOI：
10.1152/ajprenal.00319.2012
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发表时间：
2012-10-01
影响因子：
4.2
通讯作者：
Jialal, Ishwarlal
中科院分区：
文献类型：
--
作者：
Kaur, Harmeet;Chien, Alexander;Jialal, Ishwarlal
Kaur H，Chien A，Jialal I.高血压诱导小鼠系膜细胞Toll样受体4表达和活性：与糖尿病肾病的相关性。美国肾脏生理学杂志303：F1145-F1150，2012年。首次发表于2012年8月8日; doi：10.1152/ajprenal.00319.2012. -糖尿病是一种促炎症状态。模式识别受体Toll样受体（TLR）在糖尿病患者中增加，并已被认为在糖尿病肾病（DN）中发挥作用。DN的进展涉及肾小球系膜细胞（MC）功能的改变和系膜基质的扩张。有一个缺乏的数据检查TLR的作用及其在MC中的表达。我们推测系膜区TLR的表达可能是导致系膜扩张和肾病的重要因素。因此，我们在体外研究高糖对小鼠系膜细胞（MMC）TLR2和TLR4表达的影响。与5.5mM葡萄糖相比，25mM葡萄糖作用MMC 24h后，TLR4mRNA和细胞表面受体表达增加（P <0.05）。有趣的是，我们不能检测到TLR2在MMC中的表达。此外，在暴露于25 mM葡萄糖的细胞中，TLR4下游信号级联的表达显著增加（P <0.05），所述信号级联包括髓样分化因子88（MyD88）、干扰素调节因子3（IRF3）和含有衔接子诱导干扰素-β（TRIF）相关衔接子分子（TRAM）的Toll白介素受体结构域。NF-κ B活化也显著增加，同时沿着炎性细胞因子IL-6和单核细胞趋化蛋白-1分泌增加。在25mM葡萄糖存在下，转化生长因子-β的水平也显著增加（P <0.05）。总的来说，这些数据表明，高血糖激活TLR4的表达和活性在MC，并可能有助于DN。
Kaur H, Chien A, Jialal I. Hyperglycemia induces Toll like receptor 4 expression and activity in mouse mesangial cells: relevance to diabetic nephropathy. Am J Physiol Renal Physiol 303: F1145-F1150, 2012. First published August 8, 2012; doi:10.1152/ajprenal.00319.2012.-Diabetes is a proinflammatory state. The pattern recognition receptors, Toll-like receptors (TLRs), are increased in diabetic patients and have been suggested to play a role in diabetic nephropathy (DN). Progression of DN involves altered mesangial cell (MC) function with an expansion of the mesangial matrix. There is a paucity of data examining the role of TLR and its expression in MC. We hypothesize the expression of TLRs in the mesangium might be an important factor contributing to mesangium expansion and nephropathy. Thus we evaluated the effect of high glucose on TLR2 and TLR4 expression in mouse mesangial cells (MMC) in vitro. Exposure of MMC to 25 mM glucose for 24 h resulted in increased TLR4 mRNA and cell surface receptor expression compared with 5.5 mM glucose (P < 0.05). Interestingly, we were not able to detect expression of TLR2 in MMC. Furthermore, expression of a TLR4 downstream signaling cascade including myeloid differentiation factor 88 (MyD88), interferon regulatory factor 3 (IRF3), and Toll interleukin receptor domain containing adaptor inducing interferon-beta (TRIF)-related adaptor molecule (TRAM) were significantly increased in cells exposed to 25 mM glucose (P < 0.05). There was also a significant increase in NF-kappa B activation along with increased secretion of inflammatory cytokines IL-6 and monocyte chemotactic protein-1. Levels of transforming growth factor-beta were also significantly increased in the presence of 25 mM glucose (P < 0.05). Collectively, these data suggest that hyperglycemia activates TLR4 expression and activity in MC and could contribute to DN.