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Abstract: PO2487

D-Serine Promotes Kidney Remodeling via an mTOR-Related Pathway

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Hesaka, Atsushi, Kokuritsu Kenkyu Kaihatsu Hojin Iyaku Kiban Kenko Eiyo Kenkyujo, Ibaragi, Osaka, Japan
  • Isaka, Yoshitaka, Osaka Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Suita, Osaka, Japan
  • Kimura, Tomonori, Kokuritsu Kenkyu Kaihatsu Hojin Iyaku Kiban Kenko Eiyo Kenkyujo, Ibaragi, Osaka, Japan

Group or Team Name

  • NIBIOHN
Background

D-Serine, a long-term undetected enantiomer of serine, is a biomarker that reflects kidney function and disease activity, whereas the physiological functions of D-serine have been unclear. Here, we investigated the physiological functions of D-serine in human living kidney donors and in unilateral nephrectomy (UNX) mice model.

Methods

Dynamics of D-serine was assessed by measuring D-serine in human samples of living kidney donors using two-dimensional high-performance liquid chromatography before and after UNX. Effects of D-serine on kidney from UNX mice and genetically modified cells were examined by gene expression profiling and histological studies.

Results

Human living kidney donors after UNX decreased urinary excretion and thus increased the blood level of D-serine. The plasma ratio of D-serine correlated well with glomerular filtration rate (GFR). Treatment of D-serine at physiological dose promoted the enlargement of remnant kidney in UNX mouse model. Profiling of pathway enrichment analysis using RNAseq in the kidney of UNX mice revealed dominant activation of the cell cycle-related pathways by D-serine treatment. Mechanistically, D-serine activated the cell cycle for tissue remodeling through an mTOR-related pathway, and inhibition of mTOR suppressed D-serine-induced cellular proliferation.

Conclusion

D-Serine is a physiological molecule that promotes kidney remodeling. Besides its function as a biomarker, D-serine has a physiological activity that influences kidney function.

Funding

  • Commercial Support