Journal Article

Macrophage Dectin-1 mediates Ang II renal injury through neutrophil migration and TGF-β1 secretion

Ye, Yang, Huang, He, Luo, Wu, Fu, Guosheng, Zhao, Xia, Ye, Shiju, Wang, Yi, Liang, Guang, Shi, Fengjie, Lai, Dongwu, Huang, Weijian, Xiao, Yun, Han, Xue, Chen, Jiawen

2023

Overview

Macrophage activation has been shown to play an essential role in renal fibrosis and dysfunction in hypertensive chronic kidney disease. Dectin-1 is a pattern recognition receptor that is also involved in chronic noninfectious diseases through immune activation. However, the role of Dectin-1 in Ang II-induced renal failure is still unknown. In this study, we found that Dectin-1 expression on CD68 + macrophages was significantly elevated in the kidney after Ang II infusion. We assessed the effect of Dectin-1 on hypertensive renal injury using Dectin-1-deficient mice infused by Angiotensin II (Ang II) at 1000 ng/kg/min for 4 weeks. Ang II-induced renal dysfunction, interstitial fibrosis, and immune activation were significantly attenuated in Dectin-1-deficient mice. A Dectin-1 neutralizing antibody and Syk inhibitor (R406) were used to examine the effect and mechanism of Dectin-1/Syk signaling axle on cytokine secretion and renal fibrosis in culturing cells. Blocking Dectin-1 or inhibiting Syk significantly reduced the expression and secretion of chemokines in RAW264.7 macrophages. The in vitro data showed that the increase in TGF-β1 in macrophages enhanced the binding of P65 and its target promotor via the Ang II-induced Dectin-1/Syk pathway. Secreted TGF-β1 caused renal fibrosis in kidney cells through Smad3 activation. Thus, macrophage Dectin-1 may be involved in the activation of neutrophil migration and TGF-β1 secretion, thereby promoting kidney fibrosis and dysfunction. Graphical Abstract

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Angiotensin / Angiotensin II / Angiotensin II - metabolism / Angiotensin II - pharmacology / Animals / Antibodies / Biochemistry / Biomedical and Life Sciences / Biomedicine / Cell activation / Cell Biology / Chemokines / Fibrosis / Hypertension / Hypertension, Renal - metabolism / Hypertension, Renal - pathology / Immune response / Kidney - metabolism / Kidney diseases / Kidneys / Leukocyte migration / Leukocytes (neutrophilic) / Life Sciences / macrophage activation / Macrophages / Macrophages - metabolism / Mice / Neutrophils / Neutrophils - metabolism / Original / Original Article / Pattern recognition / Pattern recognition receptors / Renal failure / Renal function / secretion / Smad3 protein / Syk protein / Transforming Growth Factor beta1 - metabolism / Transforming growth factor-b1