Androgen Receptor Enhances Kidney Stone-CaOx Crystal Formation via Modulation of Oxalate Biosynthesis & Oxidative Stress
| Autor: | Chiung-Kuei Huang, Liang Liang, Luke S. Chang, David A. Bushinsky, Soo Ok Lee, Chawnshang Chang, Lei Li, Jing Tian, Qiang Dang, Shuyuan Yeh, Erdal Erturk, Dalin He |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Curcumin 030232 urology & nephrology Calcium oxalate medicine.disease_cause Kidney Calculi 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology medicine Animals Humans Sex Distribution Receptor Molecular Biology Original Research 030304 developmental biology Mice Knockout Sex Characteristics 0303 health sciences Kidney NADPH oxidase Calcium Oxalate biology HEK 293 cells Hep G2 Cells General Medicine medicine.disease Mice Inbred C57BL Androgen receptor Oxidative Stress HEK293 Cells medicine.anatomical_structure chemistry Biochemistry Receptors Androgen Case-Control Studies Proteolysis biology.protein Female Kidney stones Oxidative stress |
| Zdroj: | Molecular Endocrinology |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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