Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cystathionine gamma-lyase is required for the heat shock protein 70-driven penile neurovascular regeneration and erectile function recovery

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE180916 | GEO | 2022/05/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

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

Gene expression profile on the penile tissue of erectile dysfunction (ED) in cavernous nerve injury (CNI) RAT model

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

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

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

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

Gene expression profile on the penile tissue of erectile dysfunction (ED) in cavernous nerve injury (CNI) RAT model

2012-12-31 | GSE31247 | GEO

Control vs Diabetic Penile Tissues

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. Keywords: other

2005-08-23 | GSE2457 | GEO

Cystathionine gamma-lyase is required for the heat shock protein 70-driven penile neurovascular regeneration and erectile function recovery

Project description:Cystathionine gamma-lyase is required for the heat shock protein 70-driven penile neurovascular regeneration and erectile function recovery

| PRJNA750070 | ENA

Transcriptional profiling of mouse cavenous endothelial cells in normal and high glucose condition

Project description:Purpose: To investigate the potential target genes associated with diabetic condition in mouse cavernous endothelial cells (MCECs) for diabetic induced erectile dysfunction (ED) treatment. Materials and Methods: Mouse cavernous tissue was embedded into Matrigel and sprouted cells were subcultivated for other studies. To mimic diabetic condition, the MCECs were exposed to normal-glucose (NG, 5 mmoL) and high-glucose (HG, 30 mmoL) condition for 72 hours. RNA-sequencing assay was performed to evaluate gene expression profiling and RT-PCR was used for sequencing data validation.

2020-09-01 | GSE146078 | 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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data