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.
Highlights
RNA Extraction and qPCR Analysis Total RNAs were isolated from cells or tissues using Trizol reagent (Invitrogen, Grand Island, NY) according to the manufacturer’s instructions. 1 μg of total RNA was subjected to reverse transcription using Superscript III transcriptase (Invitrogen, Grand Island, NY)
In vivo part: Eight weeks old B6 WT male mice were divided into two groups (6 mice/group) and either vehicle or ASC-J9® were i.p. injected (75 mg/kg body weight, daily treatment) for 3 weeks
After 2 weeks of treatments, all mice were subjected to glyoxylate challenge (100 mg/kg/day, daily treatment), ASC-J9® or vehicle was co-injected at this time
Summary
RNA Extraction and qPCR Analysis Total RNAs were isolated from cells or tissues using Trizol reagent (Invitrogen, Grand Island, NY) according to the manufacturer’s instructions. 1 μg of total RNA was subjected to reverse transcription using Superscript III transcriptase (Invitrogen, Grand Island, NY). In vivo part: Eight weeks old B6 WT male mice were divided into two groups (6 mice/group) and either vehicle or ASC-J9® were i.p. injected (75 mg/kg body weight, daily treatment) for 3 weeks. Control mice were injected the with vehicle, N,N-dimethylacetamide (DMA). After 2 weeks of treatments, all mice were subjected to glyoxylate challenge (100 mg/kg/day, daily treatment), ASC-J9® or vehicle was co-injected at this time.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
