Atsushi Hesaka1,2,3, Yusuke Tsukamoto1,2, Shigeyuki Nada4, Masataka Kawamura5, Naotsugu Ichimaru5,6, Shinsuke Sakai1,2,3, Maiko Nakane7, Masashi Mita7, Daisuke Okuzaki8, Masato Okada4, Yoshitaka Isaka3, Tomonori Kimura1,2,3. 1. KAGAMI Project, National Institutes of Biomedical Innovation, Health and Nutrition. 2. Reverse Translational Project, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition. 3. Department of Nephrology, Osaka University Graduate School of Medicine. 4. Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University. 5. Department of Urology, Osaka University Graduate School of Medicine. 6. Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine. 7. KAGAMI Inc. 8. Genome Information Research Center, Research Institute for Microbial Disease, Osaka University.
Abstract
Background: d-serine, a long-term undetected enantiomer of serine, is a biomarker that reflects kidney function and disease activity. The physiologic functions of d-serine are unclear. Methods: The dynamics of d-serine were assessed by measuring d-serine in human samples of living kidney donors using two-dimensional high-performance liquid chromatography, and by autoradiographic studies in mice. The effects of d-serine on the kidney were examined by gene expression profiling and metabolic studies using unilateral nephrectomy mice, and genetically modified cells. Results: Unilateral nephrectomy in human living kidney donors decreases urinary excretion and thus increases the blood level of d-serine. d-serine is quickly and dominantly distributed to the kidney on injection in mice, suggesting the kidney is a main target organ. Treatment of d-serine at a low dose promotes the enlargement of remnant kidney in mouse model. Mechanistically, d-serine activates the cell cycle for tissue remodeling through an mTOR-related pathway. Conclusions: d-serine is a physiologic molecule that promotes kidney remodeling. Besides its function as a biomarker, d-serine has a physiologic activity that influences kidney function.
Background: d-serine, a long-term undetected enantiomer of serine, is a biomarker that reflects kidney function and disease activity. The physiologic functions of d-serine are unclear. Methods: The dynamics of d-serine were assessed by measuring d-serine in human samples of living kidney donors using two-dimensional high-performance liquid chromatography, and by autoradiographic studies in mice. The effects of d-serine on the kidney were examined by gene expression profiling and metabolic studies using unilateral nephrectomy mice, and genetically modified cells. Results: Unilateral nephrectomy in human living kidney donors decreases urinary excretion and thus increases the blood level of d-serine. d-serine is quickly and dominantly distributed to the kidney on injection in mice, suggesting the kidney is a main target organ. Treatment of d-serine at a low dose promotes the enlargement of remnant kidney in mouse model. Mechanistically, d-serine activates the cell cycle for tissue remodeling through an mTOR-related pathway. Conclusions: d-serine is a physiologic molecule that promotes kidney remodeling. Besides its function as a biomarker, d-serine has a physiologic activity that influences kidney function.
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