title: Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy.
abstract: Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protective role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinine (SCr) and less renal injury, together with RTEC apoptosis in females, were found. Treatment with E2 in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis. In the mice kidney tissue and human renal proximal tubule cells (HK-2 cells), E2 both attenuated AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15), p53, and cleaved-caspase-3. This study highlights that E2 exhibited protective effects on the renal injury of acute AAN in male mice by reducing RTEC apoptosis, which might be related to inhibiting the p53 signaling pathway.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. minshi0616@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Division of Nephrology, Department of Internal Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. Liang_m@scu.edu.cn.|Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. Liang_m@scu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Division of Nephrology, Department of Internal Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. zhouli126@hotmail.com.|Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. zhouli126@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Nephrology, Department of Internal Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. fupinghx@163.com.|Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. fupinghx@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D034341:Aristolochic Acids / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D034341:Aristolochic Acids; D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D003404:Creatinine; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: apoptosis; aristolochic acid nephropathy; estradiol; p53; renal tubular epithelial cell