D-Serine Mediates Cellular Proliferation for Kidney Remodeling
D-Serine Mediates Cellular Proliferation for Kidney Remodeling
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DOI：
10.34067/kid.0000832021
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发表时间：
2021-10-28
期刊：
影响因子：
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通讯作者：
Kimura, Tomonori
中科院分区：
文献类型：
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作者：
Hesaka, Atsushi;Tsukamoto, Yusuke;Kimura, Tomonori
背景D-丝氨酸是一种长期未被检测到的丝氨酸对映体，是反映肾功能和疾病活动性的生物标志物。方法采用二维液相色谱检测活体肾组织中D-丝氨酸的含量，并在小鼠体内进行放射自显影，以评价D-丝氨酸的动态变化。结果单侧肾切除小鼠肾脏切除后，D-丝氨酸排泄量减少，血D-丝氨酸水平升高。D-丝氨酸在小鼠体内注射后迅速且主要分布到肾脏，表明肾脏是主要的靶器官。小剂量D-丝氨酸治疗可促进小鼠残肾增大。结论D-丝氨酸是一种促进肾脏重塑的生理分子。除了作为生物标志物的功能外，D-丝氨酸还具有影响肾功能的生理活性。
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.