2. Academic Validation
  3. Macrophage Dectin-1 mediates Ang II renal injury through neutrophil migration and TGF-β1 secretion

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

  • Cell Mol Life Sci. 2023 Jun 20;80(7):184. doi: 10.1007/s00018-023-04826-4.
Shiju Ye # 1 2 3,  He Huang # 1,  Yun Xiao # 1,  Xue Han 2,  Fengjie Shi 1,  Wu Luo 2 4,  Jiawen Chen 1,  Yang Ye 1,  Xia Zhao 2,  Weijian Huang 3,  Yi Wang 4,  Dongwu Lai 1,  Guang Liang 5 6,  Guosheng Fu 7
Affiliations

Affiliations

  • 1 Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310020, Zhejiang, China.
  • 2 School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, 311399, Zhejiang, China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
  • 4 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
  • 5 School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, 311399, Zhejiang, China. [email protected].
  • 6 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. [email protected].
  • 7 Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310020, Zhejiang, China. [email protected].
  • # Contributed equally.
PMID: 37340199 DOI: 10.1007/s00018-023-04826-4
Abstract

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.

Keywords

Angiotensin II; Chronic kidney disease; Dectin-1; Hypertension; TGF-β1.

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