Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, NSW, Australia.
Curr Opin Nephrol Hypertens. 2018 Jan;27(1):30-34. doi: 10.1097/MNH.0000000000000377.
Involved in innate immunity, toll-like receptors (TLRs) recognize pathogenic and endogenous ligands. Ligand binding initiates an inflammatory cascade which if sustained leads to fibrosis. This review summarizes the role of TLRs in diabetic kidney disease (DKD) with particular emphasis on TLR2 and TLR4.
Collectively, preclinical evidence to date supports the causative role of TLR2 and TLR4 in both type I and type II DKD. The relative importance of each is still unclear. In experimental models, there are increased TLR2 and TLR4 ligands, expression and signalling. Functional studies using inhibitors or knockout animal models confirm causality. Clinical evidence also supports increased ligands and TLR2 and TLR4 expression in diabetes however there are no clinical studies examining whether interruption of these pathways confer renoprotection.
Preclinical evidence to date supports the role of TLR2 and TLR4 in DKD. It will be useful to examine the value of interrupting these signalling pathways in clinical trials.
天然免疫中的 toll 样受体（TLR）能够识别病原体和内源性配体。配体结合会引发炎症级联反应，如果持续存在则会导致纤维化。本综述总结了 TLR 在糖尿病肾病（DKD）中的作用，特别强调了 TLR2 和 TLR4。
目前，临床前证据支持 TLR2 和 TLR4 在 1 型和 2 型 DKD 中的致病作用。但每种受体的相对重要性尚不清楚。在实验模型中，TLR2 和 TLR4 的配体、表达和信号均增加。使用抑制剂或基因敲除动物模型进行的功能研究证实了其因果关系。临床证据也支持糖尿病患者中 TLR2 和 TLR4 表达增加以及配体增加，但尚无临床研究探讨阻断这些通路是否能提供肾脏保护作用。
目前的临床前证据支持 TLR2 和 TLR4 在 DKD 中的作用。在临床试验中检验阻断这些信号通路的价值将是有益的。
