Dataset Information

Gene expression profile comparison in the penile tissue of diabetes and cavernous nerve injury-induced erectile dysfunction rat model.

ABSTRACT:

Purpose

To investigate the effects of cavernous nerve injury (CNI) on gene expression profiles in the cavernosal tissue of a CNI-induced erectile dysfunction (ED) model and to provide a basis for future investigations to discover potential target genes for ED treatment.

Materials and methods

Young adult rats were divided randomly into 2 groups: sham operation and bilateral CN resection. At 12 weeks after CNI we measured erectile responses and performed microarray experiments and gene set enrichment analysis to reveal gene signatures that were enriched in the CNI-induced ED model. Alterations in gene signatures were compared with those in the diabetes-induced ED model. The diabetic-induced ED data is taken from GSE2457.

Results

The mean ratio of intracavernosal pressure/blood pressure for the CNI group (0.54±0.4 cmH2O) was significantly lower than that in the sham operation group (0.73±0.8 cmH2O, p<0.05). Supervised and unsupervised clustering analysis showed that the diabetes- and CNI-induced ED cavernous tissues had different gene expression profiles from normal cavernous tissues. We identified 46 genes that were upregulated and 77 genes that were downregulated in both the CNI- and diabetes-induced ED models.

Conclusions

Our genome-wide and computational studies provide the groundwork for understanding complex mechanisms and molecular signature changes in ED.

SUBMITTER: Kam SC

PROVIDER: S-EPMC4949699 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Gene expression profile comparison in the penile tissue of diabetes and cavernous nerve injury-induced erectile dysfunction rat model.

Kam Sung Chul SC Lee Sang Hoon SH Jeon Ju Hong JH So Insuk I Chae Mee Ree MR Park Jong Kwan JK Lee Sung Won SW

Investigative and clinical urology 20160712 4

<h4>Purpose</h4>To investigate the effects of cavernous nerve injury (CNI) on gene expression profiles in the cavernosal tissue of a CNI-induced erectile dysfunction (ED) model and to provide a basis for future investigations to discover potential target genes for ED treatment.<h4>Materials and methods</h4>Young adult rats were divided randomly into 2 groups: sham operation and bilateral CN resection. At 12 weeks after CNI we measured erectile responses and performed microarray experiments and g ...[more]

PMID: 27437539

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Project description:BackgroundProstate cancer is the most common solid-organ malignancy in adult men. Early detection and treatment of prostate cancer with radical prostatectomy (RP) has improved cancer-specific survival but is associated with penile shortening and erectile dysfunction. Penile traction therapy (PTT) has been demonstrated to increase stretched penile length (SPL) prior to penile prosthesis placement and may improve erectile function (EF) in patients with Peyronie's disease. We aimed to evaluate the efficacy of PTT in preserving penile length and EF after bilateral cavernous nerve crush injury (BCNI) in a rat model.MethodsTwenty-four male Sprague-Dawley rats aged 11-13 weeks were randomly assigned to three groups (n=8, each): sham operation with no PTT (Sham), BCNI without PTT (Crush), and BCNI with PTT (Traction). PTT was started on postoperative day 3. A traction force of 1 Newton was applied to the penis for 30 minutes each day for 28 days. After 28 days of traction, the cavernous nerve was stimulated while recording the intracavernosal pressure (ICP) and the mean arterial pressure (MAP) simultaneously. Cavernosal tissue was excised, and western blot analysis for endothelial nitric oxide synthase (eNOS) was performed. Significance was determined by using ANOVA with Tukey-Kruger post-hoc testing.ResultsAt 4 weeks after nerve injury, the Traction group had significantly greater SPL compared to the Sham and Crush groups (30 vs. 28 and 27 mm, respectively). The Sham group had significantly greater EF (ΔICP/MAP) compared to the Crush group at 2.5, 5, and 7.5 V. The EF of the Traction group was between that of the Sham and Crush groups and was not significantly different from the Sham group at any voltages. Further downstream analysis revealed that the Traction group had significantly greater eNOS expression in cavernosal tissue compared to the Crush group, which was confirmed on western blot analysis and immunohistochemistry (IHC) staining.ConclusionsFindings from this animal study suggest that PTT has the potential to mitigate penile retraction after RP. While more studies are needed to determine the effect of PTT on preservation of EF, the increased eNOS expression observed in the Traction group offers a potential protective mechanism of action.

Project description:PurposeErectile dysfunction (ED) is a common postoperative complication of pelvic surgery for which there is currently no effective treatment. This study investigated the therapeutic effects and potential mechanisms of adipose derived mesenchymal stem cells-derived mitochondria (ADSCs-mito) transplantation in a rat model of bilateral cavernous nerve injury (CNI) ED.Materials and methodsWe isolated mitochondria from ADSCs and tested their quality. In vivo, twenty male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI groups that received intracavernous injection of either phosphate buffer solution, ADSCs-mito or ADSCs. Two weeks after therapy, the erectile function of the rats was evaluated and the penile tissues were harvested for histologic analysis and western blotting. In vitro, the apoptosis rate, reactive oxygen species (ROS), mitochondria derived active oxygen (mtROS) and adenosine triphosphate (ATP) levels were detected in corpus cavernosum smooth muscle cells (CCSMCs) after the incubation with ADSCs-mito. In addition, intercellular mitochondrial transfer was visualized by co-culture of ADSCs and CCSMCs.ResultsThe ADSCs, ADSCs-mito and CCSMCs were isolated and identified successfully. ADSCs-mito transplantation notably restored the erectile function and smooth muscle content of CNI ED rats. Moreover, the levels of ROS, mtROS and cleaved-caspase 3 were reduced and the levels of superoxide dismutase and ATP were increased after ADSCs-mito transplantation. In CNI ED rats, the mitochondrial structure of cells in penile tissues was destroyed. ADSCs could transfer its own mitochondria to CCSMCs. Pre-treatment with ADSCs-mito could significantly decrease apoptosis rate, ROS levels and mtROS levels as well as restore the ATP level in CCSMCs.ConclusionsADSCs-mito transplantation significantly ameliorated ED induced by CNI, with similar potency to ADSCs treatment. The ADSCs-mito might exert their effects via anti-oxidative stress, anti-apoptosis and modulating energy metabolism of CCSMCs. Mitochondrial transplantation should be a promising therapeutic method for treating CNI ED in the future.

Dataset Information

Gene expression profile comparison in the penile tissue of diabetes and cavernous nerve injury-induced erectile dysfunction rat model.

Purpose

Materials and methods

Results

Conclusions

Publications

Gene expression profile comparison in the penile tissue of diabetes and cavernous nerve injury-induced erectile dysfunction rat model.

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