Glycyrrhizic acid improves tacrolimus-induced renal injury by regulating autophagy.
Rui Cao, Yakun Li, Xiaofan Hu, Yang Qiu, Shanglin Li, Yanan Xie, Cong Xu, Chenqi Lu, Gang Chen, Jun Yang
Author Information
Rui Cao: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Yakun Li: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Xiaofan Hu: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Yang Qiu: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Shanglin Li: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Yanan Xie: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Cong Xu: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Chenqi Lu: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Gang Chen: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China.
Jun Yang: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, and Key Laboratory of Organ Transplantation, Ministry of Health, Wuhan, China. ORCID
Tacrolimus (TAC)-induced renal injury is detrimental to long-term kidney function, but a treatment medication is not available. Glycyrrhizic acid (GA) is an active ingredient in licorice widely used to treat kidney disease. Thus, this study explored the mechanisms of renoprotection by GA on TAC-induced renal injury. C57BL/6 mice were subjected daily to TAC or a combination of TAC and GA for 4 weeks, and then renal function, histopathology, and autophagy were assessed to examine the effect of GA on a renal injury. Next, Human kidney proximal tubular epithelial (HK-2) cells were pretreated with GA for 2 h and then treated with TAC for 24 h. The effect of GA on TAC-induced HK-2 cell injury was assessed by measuring cell viability, apoptosis, autophagy, and lysosomes. Mice exposed to TAC and treated with GA had significantly greater improvements in renal function and tubulointerstitial fibrosis in comparison to mice not treated with GA. In addition, fibrosis-related protein expression, including α-smooth muscle actin and fibronectin, decreased after GA treatment. GA treatment also relieved autophagic clearance in TAC-induced renal injury. Several in vitro studies found that TAC inhibited cell viability, autophagy, lysosomal acidification, and promoted apoptosis. However, these results were less pronounced with GA pretreatment. In addition, bafilomycin A1 (which inhibits lysosomal function) reduced the protective effect of GA, indicating that lysosomal function plays an important role in this effect. Our data suggest that GA improves lysosomal function and regulates autophagy to protect against TAC-induced renal injury.
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Grants
81873624/National Natural Science Foundation of China (NSFC)
