Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Biochem Biophys Res Commun. 2021 Apr 16;549:75-82. doi: 10.1016/j.bbrc.2021.02.094. Epub 2021 Mar 2.
Btk has pro-inflammatory role through a variety of signaling pathways. NLRP3 inflammasome plays a central role in liver inflammation for mediating the secretion of pro-inflammatory mediators. However, it is still unknown whether Btk could regulate NLRP3 inflammasome activation in diabetic liver. In this study, we used Btk knockout mice to establish the diabetic model by STZ. We found that Btk knockout could alleviate diabetic liver injury. This protection was due to reduced liver inflammation rather than lipid metabolism. Moreover, we found that macrophage infiltration and pro-inflammatory mediators were both significantly increased in diabetic mice liver. However, Btk deletion could reduce the activation of macrophage and secretion of pro-inflammatory cytokine, and reduced the liver inflammation through suppressing NLRP3 inflammasome activation. In conclusion, our study demonstrated that Btk knockout could significantly attenuate liver inflammation in diabetic mice by down-regulating NLRP3 inflammasome activation. Our finding has a broad prospect and provide a new idea for the treatment of diabetic liver injury.
Btk 通过多种信号通路发挥促炎作用。NLRP3 炎性体在介导促炎介质的分泌中在肝炎症中起核心作用。然而，Btk 是否可以调节糖尿病肝脏中的 NLRP3 炎性体激活仍然未知。在这项研究中，我们使用 Btk 敲除小鼠通过 STZ 建立糖尿病模型。我们发现 Btk 敲除可以减轻糖尿病肝损伤。这种保护作用不是由于脂质代谢，而是由于肝炎症减少。此外，我们发现糖尿病小鼠肝脏中巨噬细胞浸润和促炎介质均显著增加。然而，Btk 缺失可减少巨噬细胞的激活和促炎细胞因子的分泌，并通过抑制 NLRP3 炎性体激活减轻肝炎症。总之，我们的研究表明，Btk 敲除可通过下调 NLRP3 炎性体激活显著减轻糖尿病小鼠的肝炎症。我们的发现具有广阔的前景，并为糖尿病肝损伤的治疗提供了新的思路。
