Gene expression profile on the penile tissue of erectile dysfunction (ED) in cavernous nerve injury (CNI) RAT model
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE31247 | GEO | 2012/12/31
SECONDARY ACCESSION(S): PRJNA146055
REPOSITORIES: GEO
Similar Datasets
Project description:(Erectile dysfunction) ED during the radical prostatectomy (RP) treatment is caused by surgical injury of the cavernous nerve which is the final neuronal pathways of penile erection. We performed microarray experiment focused on theto understanding the gene signature alteration in the corporal cavernous tissue of the CNI-induced ED rat model. A total of 6 adult male Sprague-Dawley rats were randomly divided into two groups, sham operation (n=3) and bilateral CN resection (n=3) group. At 12 weeks after CN resection, penile tissue was harvested and microarray experiment was performed.
2012-12-31 | E-GEOD-31247 | biostudies-arrayexpress
Project description:Phosphodiesterase type 5 inhibitors (PDE5is) are the primary therapeutic option for erectile dysfunction. However, 30% of patients do not respond to PDE5is treatment, making the quest for a new treatment modality a central endeavor. Here, we found a new pathway in erectile function control, mechano-regulated YAP/TAZ activate Adrenomedullin transcription, which sustains smooth muscle cells (SMCs) relaxation to maintain the erection. We first found that penile erection stretches the SMCs, dominating YAP/TAZ activity. Subsequently, we showed that YAP/TAZ plays a vital role in erectile function and penile rehabilitation using genetic lesions and several animal models. The mechanism relies on the regulation of Adrenomedullin on penile SMCs contraction, which we identify here as a direct YAP/TAZ transcript. Notably, conventional PDE5is targeting NO-cGMP signaling do not cure YAP/TAZ deficient ED. In contrast, by activating YAP/TAZ-Adrenomedullin cascade, mechano-stimulation improved erectile function, including PDE5is non-responders in both experimental models and clinical trials. Our studies lay the groundwork for exploring mechano-YAP/TAZ-Adrenomedullin as prospective targets in the treatment of ED
2023-03-31 | GSE208293 | GEO
Project description:Background: There is growing evidence that circular RNAs (circRNAs) play an important role in a variety of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover new circRNAs, investigate their potential role in the pathogenesis of CNI-ED, and construct a circRNA-miRNA-mRNA network. Methods: Twelve male Sprague Dawley rats were randomly divided into bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression profiles of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for real-time polymerase chain reaction (RT-qPCR). The circRNA-miRNA-mRNA network was established using Cytoscape. Gene ontology (GO)-term and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the edgeR package. Results: RNA transcriptome sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR. The ceRNA network contained 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs, including ten circRNAs, six miRNAs, and 227 mRNAs. GO analysis suggested that these ten circRNAs could regulate various processes, such as oxidation-reduction processes, lipid metabolic processes, apoptotic processes, and proteolysis. Furthermore, KEGG analysis of mRNAs in the ceRNA network showed that they were involved in energy metabolism and communication between cells. A protein‐protein interaction network was constructed with the 227 mRNAs, and five hub genes (Ccna2, Cxcl10, Pld1, Mapk11, and Mboat2) were identified. In addition, Using circRNADb, we found 12 circRNAs with protein-coding potential, three of which were highly conserved in humans and rats. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.
2022-02-09 | GSE176099 | GEO
Project description:Neurovascular dysfunction in penis is a fundamental reason of erectile dysfunction. Diabetes mellitus is one of the major causes of erectile dysfunction and leads to a poor response to oral phosphodiesterase-5 inhibitors. Heat shock protein 70 (Hsp70), a ubiquitous molecular chaperone exist in all living organisms, is known to play a role in cell survival and neuroprotection. Here, we report an effectiveness of Hsp70 in mediating neurovascular regeneration in diabetic conditions. Using Hsp70-Tg mice or Hsp70 protein administration, we demonstrate that overexpression of Hsp70 in diabetic mice restores erectile function through enhanced penile angiogenesis and neural regeneration. We found that cystathionine gamma-lyase (Cse) is a novel target of Hsp70-driven penile angiogenesis and neural regeneration. Hsp70-Cse triggered SDF1/HO-1/PI3K/Akt/eNOS/NF-κB p65 pathways involved in angiogenesis and neural regeneration. Coimmunoprecipitation and His-Tag pull down assay using mouse cavernous endothelial cells treated with Hsp70 showed the physical interaction between Hsp70 and Cse, and solid-phase binding assay revealed a high-affinity Hsp70-Cse binding with an apparent dissociation constant of 1.8 nmol/L. We provide a novel and solid evidence for Cse-dependent mechanism of Hsp70, which mediates Hsp70-induced neurovascular regeneration and the restoration of erectile function under diabetic conditions.
2022-05-11 | GSE180916 | GEO
Project description:Diabetes mellitus is one of the main causes of erectile dysfunction (ED). Due to neurovascular dysfunction, men with diabetic ED do not respond well to oral phosphodiesterase 5 inhibitors. Pericyte-derived extracellular vesicles-mimetic nanovesicles (PC-NVs) are known to play a role in promoting nerve regeneration in a mouse model of cavernous nerve injury. Here, we report that administration of PC-NVs can effectively promote penile angiogenesis and neural regeneration, thereby improving erectile function under diabetic conditions. We found that PC-NVs can induce endothelial proliferation, migration, and reduce cell apoptosis under diabetic conditions. In addition, PC-NVs induce neural regeneration in STZ-induced diabetic mice in vivo and ex vivo MPG or DRG explants under high-glucose conditions. We found that Lipocalin 2 (Lcn2) is a new target of PC-NVs in this process, indicating that PC-NVs exert their angiogenesis and nerve regeneration effects by activating MAP kinase, PI3K/Akt and suppressing P53 signaling pathway in an Lcn2-dependent manner under diabetic conditions. Our findings provide new conclusive evidence that PC-NVs mediate neurovascular regeneration and erectile function recovery under diabetic conditions through an Lcn2-dependent mechanism. Local administration of PC-NVs may be a promising treatment strategy for the treatment of diabetic ED.
2022-07-13 | GSE183220 | GEO
Project description:Purpose: To investigate the regulatory role of microRNA (miR)-148a-3p in mouse corpus cavernous pericyte (MCPs)-derived extracellular vesicles (EVs) in the treatment of diabetes-induced erectile dysfunction (ED). Materials and Methods: Mouse corpus cavernous tissue was used for MCPs primary culture and EVs isolation. Small RNA sequencing analysis was performed to assess the type and content of miRs in MCPs-EVs. Four groups of mice were used: control nondiabetic mice and streptozotocin-induced diabetic mice receiving two intracavernous injections (days -3 and 0) of phosphate buffered saline, MCPs-EVs transfected with regent control, or MCPs-EVs transfected with miR-148a-3p inhibitor. The function of miR-148a-3p in MCPs-EVs was evaluated by tube formation assay, migration assay, TUNEL assay, intracavernous pressure, immunofluorescence staining, and western blot experiments. Results: We extracted EVs from MCPs and by small RNA sequencing analysis we found that miR-148a-3p is enriched in MCPs-EVs. Exogenous administration of MCPs-EVs can effectively promote mouse cavernous endothelial cell (MCECs) tube formation, migration, proliferation, and reduce MCECs apoptosis under high-glucose conditions. However, these effects are significantly attenuated in miR-148a-3p-depleted MCPs-EVs, which is extracted after inhibiting miR-148a-3p expression in MCPs. Repeated intracavernous injections of MCPs-EVs improves erectile function by inducing cavernous neurovascular regeneration in diabetic mice. Through online bioinformatics databases and luciferase report assays, we predict Pyruvate dehydrogenase kinase-4 (PDK4) is a potential target gene of miR-148a-3p. Conclusions: Our findings provide new and reliable evidence that miR-148a-3p in MCPs-EVs significantly enhances cavernous neurovascular regeneration by inhibiting PDK4 in diabetic mice.
2023-12-19 | GSE195533 | GEO
Project description:Gene expression profile on the penile tissue of erectile dysfunction (ED) in cavernous nerve injury (CNI) RAT model
| PRJNA146055 | ENA
Project description:Purpose: Molecular mechanisms of penile corpus cavernosum aging and male age-related erectile dysfunction (ED) remain unclear. Here we profiled young and old rat penile corpus cavernousm by single-cell RNA sequencing (scRNA-seq). Methods:To map the single-cell transcriptomic landscape of penile corpus cavernosum during aging, we performed uniform manifold approximation and projection (UMAP), differential gene expression analysis (DGEs), pseudotime analysis and single-cell entropy algorithm to dissect cellular composition and transcriptional heterogeneity. For validation analysis, we further performed immunofluorescence studies on key molecules involved during penile corpus cavernosum aging. Results: After stringent filtering,transcriptomes of 14,879 single cells (8,557 young and 6,322 old) derived from penile corpus cavernosum of 5 young (3 months) and 5 old (23 months) rats were analyzed subsequently. Clustering analysis of cell-type specific gene expression identified 19 cell types, such as smooth muscle cells, endothelial cells, fibroblasts,myofibroblasts and immune cells.Transcriptomic analyses revealed that transcriptional alterations across all cell types exhibited distinct properties rather than universally consistent. DGEs analysis demonstrated that genes related to extracellular matrix organization were highly expressed. Among these cell types, fibroblasts showed apparent heterogeneities. By performing pseudotime and single-cell entropy analysis on fibroblasts, we observed the age-associated decrease of entropy, and aged fibroblasts were found to adopt senescent secretory phenotype, as evidenced by the high expression of genes associated with the senescence-associated secretory phenotype (SASP). Since eliminating senescent cells or SASP were demonstrated to improve health and life span, we further investigated the distinct senescence-related gene expression signatures across all cell types during aging. Conclusions: We plotted a cellular atlas of penile corpus cavernosum, and revealed the molecular alterations of aging cells, especially fibroblasts. Our work will deepen the understanding of the heterogeneity among certain cell types during penile corpus cavernosum aging and provide novel entry points for the age-associated ED treatment.
2022-12-07 | GSE168545 | GEO
Project description:Corpora cavernosa fibroblasts mediate penile erection
| PRJNA1049437 | ENA
Project description:Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed, which enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. We used scRNAseq to investigate fibroblast heterogeneity in the penis.
2024-03-01 | GSE249526 | GEO