1. The protective role of Nrf2 against aristolochic acid-induced renal tubular epithelial cell injury.
- Author
-
Huang X, Wu J, Liu X, Wu H, Fan J, and Yang X
- Subjects
- Acute Kidney Injury chemically induced, Acute Kidney Injury metabolism, Acute Kidney Injury pathology, Animals, Cell Line, Epithelial Cells metabolism, Epithelial Cells pathology, Heme Oxygenase (Decyclizing) genetics, Heme Oxygenase (Decyclizing) metabolism, Kidney Tubules metabolism, Kidney Tubules pathology, NAD(P)H Dehydrogenase (Quinone) genetics, NAD(P)H Dehydrogenase (Quinone) metabolism, NF-E2-Related Factor 2 genetics, Oxidative Stress drug effects, Rats, Reactive Oxygen Species metabolism, Signal Transduction, Acute Kidney Injury prevention & control, Apoptosis drug effects, Aristolochic Acids toxicity, Epithelial Cells drug effects, Kidney Tubules drug effects, NF-E2-Related Factor 2 metabolism
- Abstract
Aristolochic acid nephropathy is a rapidly progressive tubulointerstitial disease induced by aristolochic acid (AA) and effective treatment is lacking. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been proven to be protective in acute kidney injury and chronic kidney disease progression. But its role in AA-induced renal tubular epithelial cell injury has not been determined. This study aimed to investigate the role of Nrf2 in AA-induced renal tubular epithelial cell injury in vitro . NRK-52E cells were incubated with 5-50 μM AA to evaluate cell viability, reactive oxygen species (ROS) production, cell apoptosis/necrosis, and Nrf2 signaling pathway protein levels. We found that AA reduced cell viability and induced cell apoptosis in a time-dependent manner, accompanied by increased production of intracellular ROS. Meanwhile, the expression of Nrf2 signaling pathway proteins was significantly decreased. Downregulation of Nrf2 by Nrf2 siRNA decreased its downstream antioxidant proteins HO-1 and NQO1 and resulted in increased AA-induced ROS production and cell death. On the contrary, overexpression of Nrf2 increased HO-1 and NQO1 expression and resulted in decreased cell death. In conclusion, Nrf2 plays an important role in AA-induced injury. Enhanced Nrf2 signaling pathway could ameliorate AA-induced renal tubular epithelial cell injury, while downregulation of Nrf2 signaling exacerbated the injury.
- Published
- 2020
- Full Text
- View/download PDF