d-Serine Mediates Cellular Proliferation for Kidney Remodeling.

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.