α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction

Abstract

Background: Recent clinical studies have shown that proteinuria is a critical factor in the progression of chronic kidney disease (CKD) and onset of cardiovascular disease (CVD). Inflammation and infiltration of macrophages into renal tissue are implicated as a cause of proteinuria. α1-acid glycoprotein (AGP), an acute phase plasma protein, is leaked into the urine in the patients with proteinuria. However, the relationship among the urinary leakage of AGP, renal inflammation and proteinuria remains unclear. Methods: Human AGP (hAGP) was exogenously administrated for five consecutive days to adriamycin-induced nephropathy model mice. Results: Adriamycin treatment increased urinary AGP accompanied by decreasing plasma AGP in mice. Exogenous hAGP administration to adriamycin-treated mice suppressed proteinuria, renal histological injury and inflammation. Then, hAGP administration increased renal CD163 expression, a marker of anti-inflammatory macrophages. Similar changes was observed in phorbol 12-myristate 13-acetatedifferentiated THP-1 cells treated with hAGP. Even in the presence of lipopolysaccharide, 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 glomerulus disease. Thus, AGP supplementation could be a possible new therapeutic intervention for patients with glomerular disease.

Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticles for the Treatment of Hepatitis

“…Before using the HSA in this study, HSA (albumin 25%, “Benesis”) was defatted and lyophilized as previously reported . AGP was purified from supernatant of human plasma fraction V donated by KM Biologics (Kumamoto, Japan). , Edaravone (3-ethyl-1-phenyl-5-pyrazolone) was purchased from the Tokyo chemical industry (Tokyo, Japan). Radicut was purchased from Mitsubishi Tanabe Pharma (Osaka, Japan).…”

An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action

“…Human AGP was purified as previously described 24 , 26 . Briefly, human plasma fraction V supernatant provided by KM Biologics Co., Ltd. (Kumamoto, Japan) was mixed with 10 mM acetate buffer and passed through a HiTrap CM FFcolumn (5 mL) and a HiTrap Q FF column (5 mL) on an AKTAprime Plus System (GE Healthcare, Tokyo, Japan).…”

“…These data indicate that endogenous AGP may have a renal protective function. In fact, exogenous administration of human derived-AGP (hAGP) to unilateral ureteral obstruction-induced renal fibrotic mice and to adriamycin-induced nephropathy mice suppressed renal fibrosis and proteinuria by changing macrophages polarization into M2-like anti-inflammatory macrophages in the kidney 25 , 26 .…”