Lv Jinlei, Chen Qinkai, Shao Yi, Chen Yuhua, Shi Jun
Division of Nephrology, The First Affiliated Hospital of NanChang University, China.
Division of Nephrology and Organ Transplatation, The First Affiliated Hospital of NanChang University, China.
Biochem Biophys Res Commun. 2015 Apr 3;459(2):264-269. doi: 10.1016/j.bbrc.2015.02.096. Epub 2015 Feb 28.
Toll-like Receptor 4 (TLR4) may play an important role in the pathogenesis of diabetic nephropathy (DN). In this study, We observed the TLR4 signal and the release of inflammation factors after angiotensin II (Ang II) stimulation in rat mesangial cells (MCs) under high glucose conditions, this revealed the innate immune mechanism of injury by Ang II in DN. Our data showed that TLR4 and MyD88 were up-regulated significantly in high glucose and AngII-induced MCs; meanwhile, NF-κB as well as MCP-1, IL-6 were also highly expressed. In cells that were transfected with TLR4 SiRNA，the parameters were greatly inhibited; similar effects were detected in cells that were treated with Irbesartan. We concluded that Ang II synergized with high glucose in the release of pro-inflammatory factors mainly through the upregulation of TLR4 signaling in MCs, Cross-talk between Ang II and TLR4 contributed to the MC inflammatory injury under high glucose conditions.
Toll样受体4（TLR4）可能在糖尿病肾病（DN）的发病机制中起重要作用。在本研究中，我们观察了高糖条件下大鼠系膜细胞（MCs）经血管紧张素II（Ang II）刺激后的TLR4信号及炎症因子释放情况，这揭示了DN中Ang II导致损伤的固有免疫机制。我们的数据显示，在高糖和Ang II诱导的MCs中，TLR4和MyD88显著上调；同时，核因子κB（NF-κB）以及单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）也高表达。在转染了TLR4小干扰RNA（SiRNA）的细胞中，这些参数受到显著抑制；在用厄贝沙坦处理的细胞中也检测到类似效果。我们得出结论，Ang II与高糖协同作用，主要通过上调MCs中的TLR4信号来释放促炎因子，Ang II与TLR4之间的相互作用导致了高糖条件下MCs的炎症损伤。
