Single-Cell RNA-Seq Analysis of Rat Cavernous Tissue Reveals Cellular Heterogeneity and Molecular Alterations in Cavernous Nerve Injury-Induced Erectile Dysfunction
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PROVIDER: PRJNA1268208 | ENA |
REPOSITORIES: ENA
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Project description:Erectile dysfunction (ED) secondary to cavernous nerve injury (CNI) is a common complication of pelvic surgeries, yet its cellular pathophysiology remains incompletely characterized. Here, we generated a high-resolution single-cell transcriptomic atlas of rat cavernous tissue following CNI. Our analysis identified dysregulated gene networks in key cell populations (e.g., fibroblast, endothelial cells, smooth muscle cells, Schwann cells, and macrophages) associated with fibrosis, vascular dysfunction, and axonal degeneration. This dataset provides a foundation for understanding CNI-mediated ED and discovering targets for nerve regeneration and tissue repair.
2025-06-01 | GSE298059 | GEO
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:(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.
2012-12-31 | GSE31247 | 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 analysis in control and diabetic rats. Diabetes-induced erectile dysfunction in rat model of DM. 10 weeks of streptozotocin induced diabetes. F344 Rats.
2007-10-08 | E-GEOD-2457 | 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: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:The Role of Mechanoregulated YAP/TAZ in Erectile Dysfunction
| PRJNA859137 | ENA
Project description:Background: Erectile dysfunction (ED) is a prevalent male sexual disorder, commonly associated with hypertension, though the underlying mechanisms remain poorly understood. Objective: This study aims to explore the role of Fatty acid synthase (Fasn) in hypertension-induced ED and evaluate the therapeutic potential of the Fasn inhibitor C75. Materials and Methods: Erectile function was assessed by determining the intracavernous pressure/ mean arterial pressure (ICP/MAP) ratio, followed by the collection of cavernous tissue for transcriptomic and non-targeted metabolomic analyses. In vitro, a concentration of 10-6 M angiotensin II (Ang II) was applied to rat aortic endothelial cells (RAOECs) to establish a model of hypertension. In vivo, spontaneously hypertensive rats (SHR) were randomly divided into two groups. The SHR+C75 group received intraperitoneal injections of C75 at a dose of 2 mg/kg once a week. After five weeks of treatment, the erectile function of the rats was assessed, and penile tissues were harvested for further analysis. Molecular and protein expression were assessed using Western blotting, qRT-PCR, immunofluorescence staining, and immunohistochemistry. Results: The SHR exhibited ED, indicated by reduced maximum ICP/MAP ratios. Histologically, corpus cavernosum tissue of SHR showed elevated fibrosis and endothelial dysfunction. Additionally, increased expression of the NLRP3 inflammasome, Caspase-1, GSDMD, and the pro-inflammatory cytokines IL-1β and IL-18 was observed. Multi-omics analysis revealed significant enrichment in lipid metabolic pathways, with Fasn identified as a hub gene. In vitro, siFasn and C75 enhanced antioxidant markers Nrf2 and HO-1, reduced ROS accumulation, and suppressed NLRP3 and GSDMD levels. In vivo, C75 treatment restored endothelial function and reversed erectile dysfunction, accompanied by decreased oxidative stress and pyroptosis in the penile corpus cavernosum. Conclusion: These findings suggest that Fasn inhibition may offer a promising therapeutic strategy for hypertension-induced ED by alleviating oxidative stress and suppressing NLRP3 inflammasome-dependent endothelial cell pyroptosis via activation of the Nrf2/HO-1 pathway.
2024-12-24 | GSE285267 | GEO