title: Androgen receptor enhances kidney stone-CaOx crystal formation via modulation of oxalate biosynthesis & oxidative stress.
abstract: Males develop kidney stones far more frequently than females with a ratio of 2-3:1, suggesting that androgen receptor (AR) signaling might play a key role in the development of nephrolithiasis. Using the cre-loxP system to selectively knock out AR in glyoxylate-induced calcium oxalate (CaOx) crystal mouse models, we found that the mice lacking hepatic AR had less oxalate biosynthesis, which might lead to lower CaOx crystal formation, and that the mice lacking kidney proximal or distal epithelial AR also had lower CaOx crystal formation. We found that AR could directly up-regulate hepatic glycolate oxidase and kidney epithelial NADPH oxidase subunit p22-PHOX at the transcriptional level. This up-regulation might then increase oxalate biosynthesis and oxidative stress that resulted in induction of kidney tubular injury. Targeting AR with the AR degradation enhancer ASC-J9 led to suppression of CaOx crystal formation via modulation of oxalate biosynthesis and oxidative stress in both in vitro and in vivo studies. Taken together, these results established the roles of AR in CaOx crystal formation.
authors: Sex Hormone Research Center (L.Liang, L.Li, Q.D., L.S.C., D.H.), Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China; George H. Whipple Laboratory for Cancer Research (L.Liang, L.Li, J.T., S.O.L., Q.D., C.-K.H., S.Y., E.E., D.B., C.C.), Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York 14642; and Sex Hormone Research Center (C.C.), China Medical University/Hospital, Taichung 404, Taiwan.
authors: Liang
authors: L
authors: Liang
authors: Lei
authors: L
authors: Li
authors: Jing
authors: J
authors: Tian
authors: Soo Ok
authors: SO
authors: Lee
authors: Qiang
authors: Q
authors: Dang
authors: Chiung-Kuei
authors: CK
authors: Huang
authors: Shuyuan
authors: S
authors: Yeh
authors: Erdal
authors: E
authors: Erturk
authors: David
authors: D
authors: Bushinsky
authors: Luke S
authors: LS
authors: Chang
authors: Dalin
authors: D
authors: He
authors: Chawnshang
authors: C
authors: Chang
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism*; D016022:Case-Control Studies; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007669:Kidney Calculi / Q000453:epidemiology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D059748:Proteolysis / Q000187:drug effects; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics; D017678:Sex Distribution
chemical_list: D002129:Calcium Oxalate; D003474:Curcumin; D011944:Receptors, Androgen; C471106:ASC-J9 compound