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Enhanced Bruton's tyrosine kinase activity in the kidney of patients with IgA nephropathy.
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- Author(s): Wei J;Wei J; Wang Y; Wang Y; Qi X; Qi X; Wu Y; Wu Y
- Source:
International urology and nephrology [Int Urol Nephrol] 2021 Jul; Vol. 53 (7), pp. 1399-1415. Date of Electronic Publication: 2021 Jan 03.- Publication Type:
Journal Article- Language:
English - Source:
- Additional Information
- Source: Publisher: Springer Country of Publication: Netherlands NLM ID: 0262521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2584 (Electronic) Linking ISSN: 03011623 NLM ISO Abbreviation: Int Urol Nephrol Subsets: MEDLINE
- Publication Information: Publication: Amsterdam : Springer
Original Publication: Budapest, Akademiai Kiadó - Subject Terms:
- Abstract: Purpose: Bruton's tyrosine kinase (BTK) is a vital biological molecule that contributes to immune regulation. Previous studies have showed that BTK can be detected in patients with lupus nephritis and rheumatoid arthritis. However, the role of BTK in IgA nephropathy (IgAN) has not yet been elucidated. The purpose of this research was to investigate the role of BTK activation in macrophages in IgAN.
Methods: Peripheral blood and renal tissue samples were collected from 63 patients with IgAN, and peritumoral normal tissues were collected from 20 patients after surgical resection of renal tumor for use as control. Additionally, 20 healthy volunteers were recruited as control. The levels of BTK, CD68, phosphorylated BTK (pBTK), phosphorylated NF-κB (p-NF-κB p65), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and monocyte chemotactic protein (MCP)-1 were measured by immunohistochemistry (IHC), real-time polymerase chain reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA).
Results: Compared to peritumoral normal tissues, the expression levels of CD68 and BTK were significantly increased in IgAN group (p < 0.001) and the differences between M0 and M1, E0 and E1, S0 and S1, T0 and T1-2, C0 and C1-2 were statistically significant in the updated Oxford Classification (p < 0.05). Also, CD68 and BTK were positively correlated with Katafuchi semi-quantitative glomerular and tubulointerstitial scores (r = 0.580, 0.637 and 0.442, 0.489, respectively, p < 0.05). The expression of BTK was significantly higher in C3b- and C4d-positive renal tissues of patients with IgAN (p < 0.05). In addition, BTK was positively correlated with 24-h urine protein, serum creatinine levels (r = 0.456 and 0.453, respectively, p < 0.001), and negatively correlated with serum albumin (r = 0.357, p < 0.05). The intensity of expression of pBTK and p-NF-κB p65 was observably increased in renal tissues and monocytes of patients with IgAN compared to the control group. The results of IHC, RT-PCR, and ELISA indicated that the levels of TNF-ɑ, IL-1β, and MCP-1 were markedly increased in the IgAN group (p < 0.05).
Conclusion: The results of this study indicate that activation of BTK in macrophages may play an important role in promoting the progression of renal inflammation in IgAN. - References: Autoimmun Rev. 2010 Mar;9(5):A366-71. (PMID: 19906361)
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J Immunol. 2013 Nov 1;191(9):4540-50. (PMID: 24068666) - Contributed Indexing: Keywords: Bruton’s tyrosine kinase; IgA nephropathy; Katafuchi semi-quantitative score; Macrophage; NF-κb; Oxford classification
- Accession Number: EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
EC 2.7.10.2 (BTK protein, human) - Publication Date: Date Created: 20210103 Date Completed: 20211126 Latest Revision: 20211126
- Publication Date: 20231215
- Accession Number: PMC8192408
- Accession Number: 10.1007/s11255-020-02733-2
- Accession Number: 33389462
- Source:
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