Abstract: PO0430
Scaffold Protein Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) Protect Tenofovir-Induced Nephrotoxicity by Regulating Na+/Pi Cotransporter (Npt) and Intracellular Phosphorus Balance
Session Information
- AKI: Repair and Progression
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Ma, Tiantian, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Shi, Xiaoxiao, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Zhao, Bingbin, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Li, Jiaying, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Ji, Peili, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Chen, Limeng, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
Background
Tenofovir disoproxil fumarate (TDF) could cause proximal tubular (PT) dysfunctions and eGFR decline with mitochondria damages. PDZK1, MAP17, and NHERF1 are scaffold proteins that influence the localization and function of membrane proteins. We tried to investigate the changes of both membrane-associated proteins and proximal tubular transporters in TDF-induced nephrotoxic model.
Methods
C57/BL6 mice (n = 8) were gavaged daily with 10mg/kg/d, 50mg/kg/d of TDF for 8 weeks. The human renal tubular epithelial cells (HK-2) were grown and received 24 to 72 h exposure to 0–128 µM TDF or vehicle. NHERF1 was overexpressed in HK-2.
Results
Chronic TDF administration to mice resulted in swollen and exfoliated tubular epithelial cells, brush border cilia lodging and dissolving, and serum creatinine elevation (P<0.05, mean 10.23±2.683 vs. 27.18±18.41) compared to the control group. The protein expressions of scaffold protein NHERF1, Na+/Pi cotransporter (Npt), and sodium-glucose cotransporter type 2 (SGLT-2), but not PDZK1 and MAP17 were decreased in the kidneys of TDF-treated mice and cells. The intracellular phosphorus concentrations decreased dose-dependent with TDF concentration and the exposing time, companies with down-regulated Npt expressions. ATP levels reflected mitochondrial functions were also decreased with a time and dose-dependent exposure of TDF. NHERF1 overexpressing cells are well resistant to transporter damage and mitochondrial damage caused by TDF.
Conclusion
NHERF1 protects the TDF-induced AKI by Npt, intracellular phosphorus, and mitochondria dysfunction pathway.
Figure 1. Representative light micrographs and electron micrographs of mice kidney.