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Pericyte-derived extracellular vesicle-mimetic nanovesicles ameliorates erectile dysfunction through Lipocalin 2 in the diabetic mice

ABSTRACT: Pericyte-derived extracellular vesicle-mimetic nanovesicles ameliorates erectile dysfunction through Lipocalin 2 in the diabetic mice

PROVIDER: PRJNA759633 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15691823_1.fastq.gz	Fastqsanger.gz
	SRR15691823_2.fastq.gz	Fastqsanger.gz
	SRR15691824_1.fastq.gz	Fastqsanger.gz
	SRR15691824_2.fastq.gz	Fastqsanger.gz

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Similar Datasets

Pericyte-derived extracellular vesicle-mimetic nanovesicles ameliorates erectile dysfunction through Lipocalin 2 in the diabetic mice

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

Transcriptional profiling of human fibroblasts cells from normal, PD patient, and PD patient treatment with mouse cavernous pericyte-derived extracellular vesicles-mimetic nanovesicles (PC-NVs)

Project description:Peyronie’s disease (PD) is a severe fibrotic diseases in the tunica albuginea that causes penis curvatures and leads to penile pain, deformity as well as erectile dysfunction (ED). The role of pericytes in the pathogenesis of fibrosis have been perceived recently. Extracellular vesicles (EVs)-mimetic nanovesicles (NVs) have emerged particular interest in intercellular communication between cells in various fields of fibrosis disease. However, the global gene expression of pericytes-derived EVs-mimetic NVs in regulating fibrosis remains unknown. Here we used RNA-sequencing technology to investigate the potential target genes regulated by pericytes-derived EVs-mimetic NVs in primary fibroblasts derived from human PD plaque.

2021-07-07 | GSE146500 | GEO

Pericyte-derived extracellular vesicle-mimetic nanovesicles ameliorate erectile dysfunction via lipocalin 2 in diabetic mice.

Project description:Diabetes mellitus is one of the main causes of erectile dysfunction (ED). Men with diabetic ED do not respond well to oral phosphodiesterase-5 inhibitors owing to neurovascular dysfunction. Pericyte-derived extracellular vesicle-mimetic nanovesicles (PC-NVs) are known to promote nerve regeneration in a mouse model of cavernous nerve injury. Here, we report that administration of PC-NVs effectively promoted penile angiogenesis and neural regeneration under diabetic conditions, thereby improving erectile function. Specifically, PC-NVs induced endothelial proliferation and migration and reduced cell apoptosis under diabetic conditions. In addition, PC-NVs induced neural regeneration in STZ-induced diabetic mice in dorsal root ganglion and major pelvic ganglion explants in vivo and ex vivo under high-glucose conditions. We found that lipocalin 2 (Lcn2) is a new target of PC-NVs in this process, demonstrating that PC-NVs exert their angiogenic and nerve-regeneration effects by activating MAP kinase and PI3K/Akt and suppressing P53 signaling pathway in an Lcn2-dependent manner. Our findings provide new conclusive evidence that PC-NVs can promote neurovascular regeneration and recovery of erectile function under diabetic conditions via an Lcn2-dependent mechanism. Thus, local administration of PC-NVs may be a promising treatment strategy for the treatment of diabetic ED.

| S-EPMC9254477 | biostudies-literature

Employment of exosome-mimetic nanovesicles as a plasma adjuvant for cancer targeting through Golgi stress-associated ferroptosis

Project description:Plasma oncology is a promising therapeutic method that employs ionized gas to selectively target cancer cells. However, despite its efficacy in directly exposing external cancer cells to plasma, a stable delivery method through the circulatory system to internal cancer cells has yet to be developed. In this study, we revealed that bioinspired exosome-mimetic nanovesicles (EMs) can serve as a plasma adjuvant to enhance the anti-cancer effect. EM treatment increased the half-life of plasma reactive species such as nitrogen oxide in solution, thereby increasing the cytotoxicity towards cancer cells. Our syngeneic mice model experiment demonstrated that EM-treated plasma (EM-Plasma) inhibited in vivo cancer growth more efficiently than conventional plasma administration. Furthermore, we uncovered a molecular mechanism through which EM-Plasma selectively induces cancer cell death, namely, Golgi stress-associated ferroptosis. Our study provides a promising approach for the clinical application of plasma oncology in cancer treatment.

2024-05-03 | GSE231561 | GEO

Transcriptional profiling of human fibroblasts cells from normal, PD patient, and PD patient treatment with mouse cavernous pericyte-derived extracellular vesicles-mimetic nanovesicles (PC-NVs)

Project description:Transcriptional profiling of human fibroblasts cells from normal, PD patient, and PD patient treatment with mouse cavernous pericyte-derived extracellular vesicles-mimetic nanovesicles (PC-NVs)

| PRJNA610766 | ENA

MicroRNA-148a-3p in pericyte-derived extracellular vesicles improves erectile function in diabetic mice by promoting cavernous neurovascular regeneration

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

Employment of exosome-mimetic nanovesicles as a plasma adjuvant for cancer targeting through Golgi stress-associated ferroptosis

Project description:Employment of exosome-mimetic nanovesicles as a plasma adjuvant for cancer targeting through Golgi stress-associated ferroptosis

| PRJNA966970 | ENA

The Role of Mechanoregulated YAP/TAZ in Erectile Dysfunction

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

MicroRNA-148a-3p in pericyte-derived extracellular vesicles improves erectile function in diabetic mice by promoting cavernous neurovascular regeneration

Project description:MicroRNA-148a-3p in pericyte-derived extracellular vesicles improves erectile function in diabetic mice by promoting cavernous neurovascular regeneration

| PRJNA801138 | ENA

Transcription profiling of rat penis samples from animals with diabetes-induced erectile dysfunction

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

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