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Bruton's tyrosine kinase knockout in macrophages attenuates diabetic kidney disease in the streptozotocin-induced mice / 中华肾脏病杂志
Chinese Journal of Nephrology ; (12): 131-138, 2020.
Article in Chinese | WPRIM | ID: wpr-799545
Responsible library: WPRO
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.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Nephrology Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Nephrology Year: 2020 Type: Article