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α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction
Rui Fujimura1,2, Hiroshi Watanabe1, Kento Nishida1
1Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Insights
Alpha-1 acid glycoprotein (AGP) reduces proteinuria and kidney damage in mice by promoting anti-inflammatory macrophages. This suggests AGP supplementation may be a novel therapy for glomerular diseases.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Proteinuria is a key factor in chronic kidney disease (CKD) progression and cardiovascular disease.
- Inflammation and macrophage infiltration in renal tissue contribute to proteinuria.
- Alpha-1 acid glycoprotein (AGP) leaks into urine in proteinuric patients, but its role in renal inflammation is unclear.
Purpose of the Study:
- To investigate the relationship between urinary AGP, renal inflammation, and proteinuria.
- To determine if exogenous AGP administration can mitigate kidney injury and inflammation.
Main Methods:
- Adriamycin-induced nephropathy model in mice.
- Administration of human AGP (hAGP) to model mice.
- Analysis of urinary and plasma AGP levels, proteinuria, renal histology, and macrophage markers (CD163, IL-10).
Main Results:
- Adriamycin increased urinary AGP and decreased plasma AGP.
- hAGP administration suppressed proteinuria, renal injury, and inflammation in mice.
- hAGP increased CD163 expression on macrophages and IL-10 in differentiated THP-1 cells, indicating an anti-inflammatory effect.
Conclusions:
- AGP alleviates proteinuria and kidney injury by inducing anti-inflammatory macrophages.
- Endogenous AGP may protect against glomerular disease.
- AGP supplementation represents a potential therapeutic strategy for glomerular diseases.
Background:
Recent clinical studies have shown that proteinuria is a critical factor in the progression of CKD and onset of cardiovascular disease. Inflammation and infiltration of macrophages into renal tissue are implicated as causes of proteinuria. α1-Acid glycoprotein (AGP), an acute-phase plasma protein, is leaked into the urine in patients with proteinuria. However, the relationship between urinary leakage of AGP, renal inflammation, and proteinuria remains unclear.
Methods:
Human AGP (hAGP) was exogenously administrated for 5 consecutive days to adriamycin-induced nephropathy model mice.
Results:
Adriamycin treatment increased urinary AGP, accompanied by decreased plasma AGP in mice. Exogenous hAGP administration to adriamycin-treated mice suppressed proteinuria, renal histologic injury, and inflammation. hAGP administration increased renal CD163 expression, a marker of anti-inflammatory macrophages. Similar changes were observed in PMA-differentiated THP-1 cells treated with hAGP. Even in the presence of LPS, hAGP treatment increased CD163/IL-10 expression in differentiated THP-1 cells.
Conclusions:
AGP alleviates proteinuria and renal injury in mice with proteinuric kidney disease via induction of CD163-expressing macrophages with anti-inflammatory function. The results demonstrate that endogenous AGP could work to protect against glomerular disease. Thus, AGP supplementation could be a possible new therapeutic intervention for patients with glomerular disease.
