Rui Fujimura1,2, Hiroshi Watanabe1, Kento Nishida1, Yukio Fujiwara3, Tomoaki Koga4, Jing Bi1,2, Tadashi Imafuku1,2, Kazuki Kobayashi1, Hisakazu Komori1, Masako Miyahisa1, Hitoshi Maeda1, Motoko Tanaka5, Kazutaka Matsushita5, Takashi Wada6, Masafumi Fukagawa7, Toru Maruyama1. 1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. 2. Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Global Oriented) Program," Kumamoto University, Kumamoto, Japan. 3. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 4. Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. 5. Department of Nephrology, Akebono Clinic, Kumamoto, Japan. 6. Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. 7. Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Kanagawa, Japan.
Abstract
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.
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.
Authors: M A Daemen; V H Heemskerk; C van't Veer; G Denecker; T G Wolfs; P Vandenabeele; W A Buurman Journal: Circulation Date: 2000-09-19 Impact factor: 29.690
Authors: Perla Abigail Alvarado-Vazquez; Laura Bernal; Candler A Paige; Rachel L Grosick; Carolina Moracho Vilrriales; David Wilson Ferreira; Cristina Ulecia-Morón; E Alfonso Romero-Sandoval Journal: Immunobiology Date: 2017-05-16 Impact factor: 3.144