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Abstract: FR-PO395

Gut Flora-Dependent Metabolite Trimethylamine-N-Oxide Accelerates Kidney Aging Through p53/p21/Rb Pathway and Age-Related CircRNAs

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Gao, Fanfan, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, Shaanxi, China
  • Jiang, Hongli, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, Shaanxi, China
Background

Gut microbiota can influence the aging process and may modulate aging-related changes in cognitive function. Trimethylamine-N-oxide (TMAO), gut microbiota-dependent metabolites, has been shown to be associated with kidney diseases and other disease. However, the relationship between TMAO and aging, especially renal aging, has not been fully elucidated.

Methods

We analyzed age-related palsma levels of TMAO and circRNAs in 3-month-old and 24-month-old C57BL/6 mice. Then HK-2 and TCMK-1 cell were incubated with different concentrations of TMAO (0, 1uM, 10uM, 100 uM, 1mM, 10mM, 100mM, 200, 500mM) for 24h, 48h and 72h to measure cell viability using a cell counting kit-8. Western blotting and qRT-PCR was used to detect the changes of related proteins and RNA after exposure to TMAO (100mM) for 48h and 72h.

Results

In the present study, we found that circulating TMAO increased with age in mice. In vitro, we demonstrated that prolonged TMAO treatment induced senescence in HK-2 and TCMK-1 cell, characterized by reduced cell proliferation, increased expression of senescence-associated β-galactosidase (SA-β-gal). Meanwhile, TMAO increased the expression of p53, p21, p16 and decreased phosphorylation of Rb expression. Furthermore, TMAO changed the expression of circRNAs.

Conclusion

In summary, these data suggest that elevated circulating TMAO during the aging process may deteriorate HK-2, TCMK-1cell senescence and renal aging, which is probably associated with the activation of the p53/p21/Rb pathway and the change of circRNAs.

Funding

  • Government Support - Non-U.S.