Kidney Week

Abstract: TH-PO376

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

Session Information

• Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

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

Buhui Liu,

• Tu, Yue, Nanjing University of Chinese Medicine, Nanjing, JIANGSU , China

Yue Tu,

• Wan, Yigang, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China

Yigang Wan,

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.