Chen Y.-H.,Graduate Institute of Integrated Medicine |
Chen Y.-H.,China Medical University at Taichung |
Chen C.-J.,Graduate Institute of Integrated Medicine |
Chen C.-J.,China Medical University at Taichung |
And 12 more authors.
Estrogen has various regulatory functions in the growth, development, and differentiation of the female urogenital system. This study investigated the roles of ERβ in stress urinary incontinence (SUI). Wild-type (ERβ+/+) and knockout (ERβ-/-) female mice were generated (aged 6-8 weeks, n=6) and urethral function and protein expression were measured. Leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in mice under urethane anesthesia. After the measurements, the urethras were removed for proteomic analysis using label-free quantitative proteomics by nano-liquid chromatography-mass spectrometry (LC-MS/MS) analysis. The interaction between these proteins was further analysed using MetaCore. Lastly, Western blot was used to confirm the candidate proteins. Compared with the ERβ+/+ group, the LPP and MUCP values of the ERβ-/- group were significantly decreased. Additionally, we identified 85 differentially expressed proteins in the urethra of ERβ-/- female mice; 57 proteins were up-regulated and 28 were down-regulated. The majority of the ERβ knockout-modified proteins were involved in cell-matrix adhesion, metabolism, immune response, signal transduction, nuclear receptor translational regelation, and muscle contraction and development. Western blot confirmed the up-regulation of myosin and collagen in urethra. By contrast, elastin was down-regulated in the ERβ-/-mice. This study is the first study to estimate protein expression changes in urethras from ERβ-/- female mice. These changes could be related to the molecular mechanism of ERβ in SUI. © 2014 Chen et al. Source
Liang L.,Xian Jiaotong University |
Liang L.,George H Whipple Laboratory For Cancer Research |
Li L.,Xian Jiaotong University |
Li L.,George H Whipple Laboratory For Cancer Research |
And 12 more authors.
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.Wefound 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. Source