Nan Xiao

Case Western Reserve University, Cleveland, Ohio, United States

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Publications (9)40.88 Total impact

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    ABSTRACT: Manganese superoxide dismutase (MnSOD) is considered a critical component of the antioxidant systems that protect against oxidative damage. We are interested in the role of oxidative stress in bladder detrusor smooth muscle (SM) in different disease states. In this study, we generated an inducible, SM-specific Sod2(-/-) mouse model to investigate the effects of MnSOD depletion on the function of the bladder. We crossbred floxed Sod2 (Sod2(lox/lox)) mice with mice containing heterozygous knock-in of a gene encoding a tamoxifen-activated Cre recombinase in the SM22α promoter locus (SM-CreER(T2)(ki)(Cre/+)). We obtained Sod2(lox/lox), SM-CreER(T2)(ki)(Cre/+) mice and injected 8-week-old males with 4-hydroxytamoxifen to induce Cre-mediated excision of the floxed Sod2 allele. Twelve weeks later, SM-specific deletion of Sod2 and depletion of MnSOD were confirmed by polymerase chain reaction, immunoblotting, and immunohistochemistry. SM-specific Sod2(-/-) mice exhibited normal growth with no gross abnormalities. A significant increase in nitrotyrosine concentration was found in bladder SM tissue of SM-specific Sod2(-/-) mice compared with both wild type mice and Sod2(+/+), SM-CreER(T2)(ki)(Cre/+) mice treated with 4-hydroxytamoxifen. Assessment of 24-hour micturition in SM-specific Sod2(-/-) mice revealed significantly higher voiding frequency compared with both wild type and SM-specific Cre controls. Conscious cystometry revealed significantly shorter intercontraction intervals and lower functional bladder capacity in SM-specific Sod2(-/-) mice compared with wild type mice. This novel model can be used for exploring the mechanistic role of oxidative stress in organs rich in SM in different pathological conditions. Copyright © 2015, American Journal of Physiology - Cell Physiology.
    AJP Cell Physiology 05/2015; 309(3):ajpcell.00046.2015. DOI:10.1152/ajpcell.00046.2015 · 3.78 Impact Factor
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    The Journal of Urology 04/2015; 193(4):e239. DOI:10.1016/j.juro.2015.02.970 · 4.47 Impact Factor
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    ABSTRACT: To determine whether diabetes mellitus- and diuresis-induced alterations in the bladder can be reversed in rats. Male Sprague-Dawley rats were randomly distributed into eight groups (n = 16 per group): 3 weeks and 11 weeks age-matched controls, 3 weeks and 11 weeks after streptozotocin-induced diabetes mellitus, 3 weeks after diabetes mellitus induction then treated with insulin for 8 weeks, 3 weeks and 11 weeks after 5% sucrose-induced diuresis, and 3 weeks after 5% sucrose-induced diuresis followed by removal of 5% sucrose for 8 weeks. Bodyweight, blood glucose and glycated hemoglobin A1c were monitored. At the designated time-points, 24-h urinary habits were examined, and cystometry was carried out in half of the animals. The bladders from the remaining animals were harvested for histological examination, and quantification of smooth muscle, urothelium and collagen components. Insulin treatment reversed hyperglycemia and polyuria in diabetic animals successfully, which was shown by normalization of blood glucose, glycated hemoglobin A1c and 24-h urinary habits. Subsequently, bodyweight, bladder weight and percentage change of bladder components (smooth muscle, collagen, urothelium) in total bladder cross-sectional area were reversed to almost normal levels, and the bladder dysfunction was mostly reversed by 8 weeks of glycemic control, seen in the cystometry study. Similar alterations and reversed effects were seen in diuretic rats without and with 5% sucrose removal, respectively. Short-term (3-week induction) diabetes- and polyuria-induced functional and morphological alterations of the bladder can mostly be reversed in rats. © 2015 The Japanese Urological Association.
    International Journal of Urology 01/2015; 22(4):n/a-n/a. DOI:10.1111/iju.12695 · 2.41 Impact Factor
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    ABSTRACT: Animal models of vaginal distention (VD) have demonstrated increased expression of chemokine (C-C motif) ligand 7 (CCL7) In this study, we investigated the expression of CCL7 in mice models of simulated birth trauma-induced urinary incontinence using VD and pudendal nerve transection (PNT). Forty-nine mice were divided into 6 groups: VD, sham VD, PNT, sham PNT, anesthesia, and age-matched controls. The urethra, vagina, and rectum were harvested for the expression of CCL7 immediately or 24 hours after assigned procedure. Venous sampling for quantification of serum CCL7 was also performed. An analysis of variance model was used to compare the relative expression of CCL7 in each group. Urethral CCL7 expression in the VD group was significantly higher than control group after 24 hours (P < 0.01). There was no difference in the urethral CCL7 expression in PNT, sham PNT, sham VD, or anesthesia groups compared with the controls. No statistically significant difference was noted in the vaginal and rectal expression of CCL7 between any of the groups except for sham PNT. Statistically significant differences were noted in the serum CCL7 expression in the VD, PNT, and sham PNT (P < 0.01 in all) groups after 24 hours compared with the control group. This study demonstrates overexpression of urethral CCL7 after VD but not PNT. This suggests that nerve injury does not contribute to the CCL7 overexpression. The overexpression of CCL7 in the serum of mice after VD suggests a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery.
    Journal of Pelvic Medicine and Surgery 10/2013; 19(6):356-61. DOI:10.1097/SPV.0b013e3182a331a9 · 1.09 Impact Factor
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    ABSTRACT: Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats.Materials and MethodsA total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder.ResultsDiabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes.Conclusions Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction.
    The Journal of Urology 03/2013; 189(3):1130-1136. DOI:10.1016/j.juro.2012.08.222 · 4.47 Impact Factor
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    ABSTRACT: The vaginal distention (VD) translational model for postpartum stress urinary incontinence (SUI) is potentially biased for use in evaluating animals with increasing phenotypic size (obesity) due to a fixed VD volume. Our study had three principle and two secondary aims. First, to examine both ex vivo and in vivo catheter pressure changes during volume distention. Secondly, to determine mean pressure at current volume standard for use as target pressure (TP) for VD under isobaric (IB) conditions. Thirdly, to demonstrate feasibility and equivalence of VD at TP versus isovolumetric (IV) standard. Secondary aims were to demonstrate decreased variability (IB vs. IV) and to review the effect of weight. Ten French modified Foley catheters were inflated sequentially to 3.0 ml while connected (both in vivo and ex vivo) to a pressure transducer. Mean result generated TP. Thirty Sprague-Dawley rats (280-300 g) were then randomized to one of three groups: IV, IB at TP, or sham VD. Student's t-test was used to compare groups' leak point pressures (LPP) and simple linear regression was used to evaluate the effect of weight as a continuous variable. Catheter pressure/volume responses were demonstrated. Calculated TP was 531 mm Hg. LPP under conditions of IB and IV were statistically equivalent and were statistically lower than Sham. Variability was not statistically different between IB and IV groups. When treated as a continuous variable, weight had no effect on LPP. VD injury based on TP is feasible and reproducible. Understanding catheter pressure dynamics is valuable for investigating alternative rat phenotypes.
    Neurourology and Urodynamics 01/2012; 31(1):190-4. DOI:10.1002/nau.21168 · 2.87 Impact Factor
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    ABSTRACT: Urinary diversion has been used as a surgical option for some bladder diseases. We developed a urinary diversion model in the rat and examined the effects of urinary diversion on the bladder. We distributed female Sprague-Dawley® rats into age matched control, sham urinary diversion and urinary diversion groups. Each group was subsequently evaluated 1 or 8 weeks after urinary diversion or sham operation. Diversion was done by surgical disconnection of the ureters from the bladder and implantation to the uterine cervix. Conscious cystometry was examined. Bladders were harvested for histological examination and quantification of smooth muscle, urothelium and collagen. Vaginal histology was assessed. Bladder muscarinic and purinergic receptor expression was examined. All rats survived the urinary diversion procedure. Bladder weight decreased in the diversion group. Cystometry showed decreased intercontractile interval and voided volume in the urinary diversion group compared to those in the control and sham operated groups. Compliance was decreased in diverted rats. Smooth muscle and urothelium were decreased as a percent of total bladder cross-sectional area. Collagen increased in 1 and 8-week diverted rats vs controls. Histological examination of the vaginal wall revealed mild swelling in 2 rats. Urinary diversion caused decreased muscarinic 3 and ligand gated purinergic 1 receptor expression but no change in muscarinic 2 or ligand gated purinergic 2 receptors. Creating a urinary diversion model by ureterovaginostomy in the rat is feasible. Urinary diversion causes distinct functional and morphometric bladder alterations.
    The Journal of urology 11/2010; 184(5):2179-85. DOI:10.1016/j.juro.2010.06.090 · 4.47 Impact Factor
  • European Urology Supplements 04/2010; 9(2):329-329. DOI:10.1016/S1569-9056(10)61032-9 · 3.37 Impact Factor
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    ABSTRACT: The natural history and the mechanisms behind the alteration of vaginal distension (VD) in a mouse model are not clear. We examined the temporal sequelae of VD and pudendal nerve transection (PNT) on leak-point pressure (LPP) and the muscular and nerve components of the urethra in mice. Seventy-two virgin female C57BL/6 mice were equally distributed into three groups. The VD group underwent VD for 1h. The PNT group received bilateral PNT. A control group underwent sham VD. Each group was divided into four subgroups of six mice for measurement of LPP at 0, 4, 10, and 20 d after VD or PNT. LPP was measured. Morphology and neurofilament-immunoreactive nerve of the urethra were assessed. LPP was decreased at 0, 4, and 10 d but not at 20 d after VD. Decreased LPP persisted to 20 d in the PNT group. The external urethral striated muscle appeared disrupted and/or wavy in two mice at 0 d, in three mice at 4 d, in one mouse at 10 d, and in one mouse in 20 d after VD. The density of neurofilament-immunoreactive nerve in the urethra was reduced at 4 and 10 d after VD, but not at 20 d, and at 4, 10, and 20 d after PNT compared with the corresponding values of the sham VD group. The limitation of this animal model is that the pelvic floor structure of the mouse is different from that of female humans. Therefore, results of this study should be carefully applied to human subjects. VD causes reversible stress urinary incontinence in female mice. Recovery of continence function following VD is associated with repair of the external urethral sphincter and reinnervation of the urethra. This mouse model will be useful for mechanistic investigation and targeting of therapeutic intervention by taking advantage of genetic manipulation.
    European Urology 04/2009; 57(3):506-12. DOI:10.1016/j.eururo.2009.03.020 · 13.94 Impact Factor

Publication Stats

36 Citations
40.88 Total Impact Points


  • 2010–2015
    • Case Western Reserve University
      • Department of Urology (University Hospitals Case Medical Center)
      Cleveland, Ohio, United States
  • 2009
    • State University of New York Upstate Medical University
      Syracuse, New York, United States