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Abstract: TH-PO376

Hyperoside Ameliorates Renal Tubular Epithelial Cells Ageing Induced by D-Galactose via Regulating m6A Modification of TFEB mRNA

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Liu, Buhui, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China
  • Tu, Yue, Nanjing University of Chinese Medicine, Nanjing, JIANGSU , China
  • Wan, Yigang, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
Background

The kidney is a typical organ that undergoes age-related tissue injury, however, there is little information on therapeutic effects underlying age-associated renal damage. Hyperoside (HYP), a component of Abelmoschus manihot, is reported to be useful for preventing premature ageing induced by D-galactose (D-gal). But its potential mechanisms remain unclear. N6-methyladenosine (m6A) mRNA modification plays a critical role in transcription factor EB (TFEB) discovered as a master regulator of autophagic function. We thereby aimed to determine whether HYP alleviates D-gal-induced renal ageing by targeting autophagic activity and m6A modification of TFEB mRNA, compared to vitamin E (VE).

Methods

Renal proximal tubular epithelial cells of rats (NRK-52E cells) were divided into the normal, the D-gal model, the low dose of HYP, the high dose of HYP and the VE groups, and treated by the different measures, respectively. More specifically, NRK-52E cells in each group were separately treated by 1% FBS or D-gal (100 mM) or D-gal (100 mM) + HYP (5 mg/L) or D-gal (100 mM) + HYP (10 mg/L) or D-gal (100 mM) + VE (50 mg/L). After intervention for 24 h, firstly, effects of D-gal on the mRNA levels of m6A and TFEB; the ageing-related protein expression levels of Klotho, P27, P16, IL-1, TGF-β and MCP-1; SA-β-gal staining and LC3 Lentiviral transfection in NRK-52E cells were detected, respectively. Secondly, effects of D-gal, HYP and VE on activation of NRK-52E cells proliferation were investigated. Finally, effects of HYP and VE on the mRNA levels of m6A and TFEB; the ageing-related protein expression levels; SA-β-gal staining and LC3 Lentiviral transfection in NRK-52E cells exposed to D-gal were examined severally.

Results

For NRK-52E cells, D-gal induced the low mRNA levels of m6A and high mRNA levels of TFEB, and caused ageing and autophagy. The co-treatment of HYP at the high dose and D-gal significantly ameliorated the ageing-related protein expression levels and LC3 protein expression. In addition, the co-treatment of HYP at the high dose and D-gal obviously increased the mRNA level of m6A and decreased the TFEB level. The VE group has the similar changes as HYP at the high dose.

Conclusion

We clarified that HYP and VE could improve D-gal-induced renal tubular cellular ageing by reducing autophagic activity and increasing m6A modification of TFEB mRNA.

Funding

  • Government Support - Non-U.S.