Bruton's tyrosine kinase knockout in macrophages attenuates diabetic kidney disease in the streptozotocin-induced mice
10.3760/cma.j.issn.1001-7097.2020.02.010
- VernacularTitle: 巨噬细胞Bruton酪氨酸激酶基因特异性敲除减轻糖尿病小鼠肾脏损害的作用及机制
- Author:
Zhichao ZHENG
1
;
Zhe FAN
;
Yonggui WU
Author Information
1. Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
- Publication Type:Journal Article
- Keywords:
Diabetic nephropathies;
Inflammation;
Macrophages;
Bruton'
s tyrosine kinase
- From:
Chinese Journal of Nephrology
2020;36(2):131-138
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether Bruton's tyrosine kinase knockout (Btk-/-) in macrophages attenuates diabetic kidney disease in the streptozotocin (STZ)-induced mice.
Methods:Macrophages-specific Btk-/- mice and control mice (C57BL/6N) were randomly divided into WT group, diabetic group, Btk-/- group and Btk-/- diabetic group. The diabetic models were induced by STZ (50 mg/kg). After 12 weeks, relevant biochemical parameters and the histological changes of kidneys were detected. The expression of macrophages marker CD68 were detected by immunofluorescence, and the immunohistochemistry was employed to detect the expression of WT1 and Nephrin on renal podocytes. In addition, the expression of fibronectin (FN), collagen type IV (IV-Col), transforming growth factor-β1 (TGF-β1), iNOS, phospho (p)-Btk, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), MAPK and NF-κB signaling pathway were detected by Western blotting. RT-PCR was used to detect the mRNA of IL-1β, TNF-α and monocyte chemotactic protein-1 (MCP-1).
Results:Compared with diabetic group, the mice in Btk-/- diabetic group had reduced albuminuria and attenuated kidney histopathology significantly, significantly increased WT1 and Nephrin, significantly decreased expression of CD68, FN, IV-Col and TGF-β1, and these changes were correlated with decreased of renal inflammatory cytokines such as IL-1β, TNF-α, MCP-1 and down-regulating MAPK and NF-κB signaling pathway (all P<0.05).
Conclusion:Macrophages-specific Btk-/- may protect the kidney of diabetic mice by reducing the expression of renal inflammatory cytokines in MAPK and NF-κB signaling pathway.
