D-Serine Mediates Cellular Proliferation for Kidney Remodeling

被引：19

作者：

Hesaka, Atsushi ^{[1
,2
,3
]}

Tsukamoto, Yusuke ^{[1
,2
]}

Nada, Shigeyuki ^{[4
]}

Kawamura, Masataka ^{[5
]}

Ichimaru, Naotsugu ^{[5
,6
]}

Sakai, Shinsuke ^{[1
,2
,3
]}

Nakane, Maiko ^{[7
]}

Mita, Masashi ^{[7
]}

Okuzaki, Daisuke ^{[8
]}

Okada, Masato ^{[4
]}

Isaka, Yoshitaka ^{[3
]}

Kimura, Tomonori ^{[1
,2
,3
]}

机构：

[1] Natl Inst Biomed Innovat Hlth & Nutr, KAGAMI Project, Ibaraki, Japan

[2] Res Natl Inst Biomed Innovat Hlth & Nutr, Ctr Rare Dis Res, Reverse Translat Project, Ibaraki, Japan

[3] Osaka Univ, Dept Nephrol, Grad Sch Med, 2-2 Yamada Oka D11, Suita, Osaka 5650871, Japan

[4] Osaka Univ, Res Inst Microbial Dis, Dept Oncogene Res, Osaka, Japan

[5] Osaka Univ, Dept Urol, Grad Sch Med, Osaka, Japan

[6] Osaka Univ, Dept Adv Technol Transplantat, Grad Sch Med, Osaka, Japan

[7] KAGAMI Inc, Ibaraki, Japan

[8] Osaka Univ, Genome Informat Res Ctr, Res Inst Microbial Dis, Osaka, Japan

来源：

KIDNEY360 | 2021年 / 2卷 / 10期

基金：

日本学术振兴会;

关键词：

PERFORMANCE LIQUID-CHROMATOGRAPHY; AMINO-ACIDS; AUTOPHAGY PROTECTS; PROXIMAL TUBULE;

D O I：

10.34067/KID.0000832021

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1611 / 1624

页数：14

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