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Neuromedin B Restores Erectile Function by Protecting the Cavernous Body and the Nitrergic Nerves from Injury in a Diabetic Rat Model.

Nishimatsu H, Suzuki E, Saito Y, Niimi A, Nomiya A, Yamada D, Homma Y - PLoS ONE (2015)

Bottom Line: As assessed by the measurement of intracavernous pressure, AdNMB injection significantly restored erectile function compared with the injection of an adenovirus expressing green fluorescent protein.Furthermore, NMB significantly stimulated the survival of SH-SY5Y cells derived from human neuroblastoma tissue with characteristics similar to neurons.Collectively, these results suggested that NMB restored erectile function via protection of the cavernous body from injury and stimulation of the survival of the associated nerves.

View Article: PubMed Central - PubMed

Affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

ABSTRACT
Erectile dysfunction (ED) is a major health problem worldwide and affects approximately 75% of diabetic patients, likely due to severely damaged cavernous body. While screening for cytokines produced by adipose tissue-derived stem cells, we detected neuromedin B (NMB). To explore a potential treatment option for ED, we examined whether NMB was capable of restoring erectile function. We also examined the potential mechanism by which NMB could restore erectile function. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. An adenovirus expressing NMB (AdNMB) was injected into the penis 6 weeks after STZ administration. Four weeks after the injection of AdNMB, erectile function, penile histology, and protein expression were analyzed. As assessed by the measurement of intracavernous pressure, AdNMB injection significantly restored erectile function compared with the injection of an adenovirus expressing green fluorescent protein. This restoration was associated with conservation of the cavernous body structure and neural nitric oxide synthase (nNOS)-expressing nerves, together with recovery of α-smooth muscle actin, vascular endothelial-cadherin, and nNOS expression. Furthermore, NMB significantly stimulated the survival of SH-SY5Y cells derived from human neuroblastoma tissue with characteristics similar to neurons. Collectively, these results suggested that NMB restored erectile function via protection of the cavernous body from injury and stimulation of the survival of the associated nerves. NMB may be useful to treat ED patients with a severely damaged cavernous body.

No MeSH data available.


Related in: MedlinePlus

Overexpression of NMB restores erectile function.AdGFP (STZ/AdGFP) and AdNMB (STZ/AdNMB) were injected into the penises of STZ-induced diabetic rats, and ICP was measured 4 weeks later. Age-matched non-diabetic control rats were also used as positive controls (PC). (A) Representative traces of ICP and systemic arterial pressure (SAP). The stimulus interval (10 s) is indicated by a solid bar. (B) Histograms comparing the ICP/MAP among the groups (n = 5 per group). * and **: P<0.01 and P<0.001, respectively vs. PC. †: P<0.001 vs. AdGFP-injection. (C) Histograms comparing the AUC/MAP (n = 5 per group). * and **: P<0.01 and P<0.001, respectively vs. PC. †: P<0.001 vs. AdGFP-injection.
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pone.0133874.g003: Overexpression of NMB restores erectile function.AdGFP (STZ/AdGFP) and AdNMB (STZ/AdNMB) were injected into the penises of STZ-induced diabetic rats, and ICP was measured 4 weeks later. Age-matched non-diabetic control rats were also used as positive controls (PC). (A) Representative traces of ICP and systemic arterial pressure (SAP). The stimulus interval (10 s) is indicated by a solid bar. (B) Histograms comparing the ICP/MAP among the groups (n = 5 per group). * and **: P<0.01 and P<0.001, respectively vs. PC. †: P<0.001 vs. AdGFP-injection. (C) Histograms comparing the AUC/MAP (n = 5 per group). * and **: P<0.01 and P<0.001, respectively vs. PC. †: P<0.001 vs. AdGFP-injection.

Mentions: The ICP was measured in order to analyze erectile function. We used STZ-induced diabetic rats with AdGFP injected into the penis as a negative control since we have previously confirmed that the AdGFP injection does not affect erectile function in diabetic rats [16]. The ICP/MAP was significantly decreased in the AdGFP-injected group as compared with the age-matched positive control group. AdNMB injection significantly restored the ICP/MAP as compared with AdGFP-injection, although not to the same level observed in the positive control group (Fig 3B). We also analyzed the ratio of the AUC to the MAP (AUC/MAP), which was also significantly decreased in the AdGFP-injected group as compared with the positive control group. The AUC/MAP was restored in the AdNMB-injected group as compared with the AdGFP-injected group, although the AUC/MAP in the AdNMB-injected group did not return to the same level observed in the positive control group (Fig 3C).


Neuromedin B Restores Erectile Function by Protecting the Cavernous Body and the Nitrergic Nerves from Injury in a Diabetic Rat Model.

Nishimatsu H, Suzuki E, Saito Y, Niimi A, Nomiya A, Yamada D, Homma Y - PLoS ONE (2015)

Overexpression of NMB restores erectile function.AdGFP (STZ/AdGFP) and AdNMB (STZ/AdNMB) were injected into the penises of STZ-induced diabetic rats, and ICP was measured 4 weeks later. Age-matched non-diabetic control rats were also used as positive controls (PC). (A) Representative traces of ICP and systemic arterial pressure (SAP). The stimulus interval (10 s) is indicated by a solid bar. (B) Histograms comparing the ICP/MAP among the groups (n = 5 per group). * and **: P<0.01 and P<0.001, respectively vs. PC. †: P<0.001 vs. AdGFP-injection. (C) Histograms comparing the AUC/MAP (n = 5 per group). * and **: P<0.01 and P<0.001, respectively vs. PC. †: P<0.001 vs. AdGFP-injection.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514746&req=5

pone.0133874.g003: Overexpression of NMB restores erectile function.AdGFP (STZ/AdGFP) and AdNMB (STZ/AdNMB) were injected into the penises of STZ-induced diabetic rats, and ICP was measured 4 weeks later. Age-matched non-diabetic control rats were also used as positive controls (PC). (A) Representative traces of ICP and systemic arterial pressure (SAP). The stimulus interval (10 s) is indicated by a solid bar. (B) Histograms comparing the ICP/MAP among the groups (n = 5 per group). * and **: P<0.01 and P<0.001, respectively vs. PC. †: P<0.001 vs. AdGFP-injection. (C) Histograms comparing the AUC/MAP (n = 5 per group). * and **: P<0.01 and P<0.001, respectively vs. PC. †: P<0.001 vs. AdGFP-injection.
Mentions: The ICP was measured in order to analyze erectile function. We used STZ-induced diabetic rats with AdGFP injected into the penis as a negative control since we have previously confirmed that the AdGFP injection does not affect erectile function in diabetic rats [16]. The ICP/MAP was significantly decreased in the AdGFP-injected group as compared with the age-matched positive control group. AdNMB injection significantly restored the ICP/MAP as compared with AdGFP-injection, although not to the same level observed in the positive control group (Fig 3B). We also analyzed the ratio of the AUC to the MAP (AUC/MAP), which was also significantly decreased in the AdGFP-injected group as compared with the positive control group. The AUC/MAP was restored in the AdNMB-injected group as compared with the AdGFP-injected group, although the AUC/MAP in the AdNMB-injected group did not return to the same level observed in the positive control group (Fig 3C).

Bottom Line: As assessed by the measurement of intracavernous pressure, AdNMB injection significantly restored erectile function compared with the injection of an adenovirus expressing green fluorescent protein.Furthermore, NMB significantly stimulated the survival of SH-SY5Y cells derived from human neuroblastoma tissue with characteristics similar to neurons.Collectively, these results suggested that NMB restored erectile function via protection of the cavernous body from injury and stimulation of the survival of the associated nerves.

View Article: PubMed Central - PubMed

Affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

ABSTRACT
Erectile dysfunction (ED) is a major health problem worldwide and affects approximately 75% of diabetic patients, likely due to severely damaged cavernous body. While screening for cytokines produced by adipose tissue-derived stem cells, we detected neuromedin B (NMB). To explore a potential treatment option for ED, we examined whether NMB was capable of restoring erectile function. We also examined the potential mechanism by which NMB could restore erectile function. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. An adenovirus expressing NMB (AdNMB) was injected into the penis 6 weeks after STZ administration. Four weeks after the injection of AdNMB, erectile function, penile histology, and protein expression were analyzed. As assessed by the measurement of intracavernous pressure, AdNMB injection significantly restored erectile function compared with the injection of an adenovirus expressing green fluorescent protein. This restoration was associated with conservation of the cavernous body structure and neural nitric oxide synthase (nNOS)-expressing nerves, together with recovery of α-smooth muscle actin, vascular endothelial-cadherin, and nNOS expression. Furthermore, NMB significantly stimulated the survival of SH-SY5Y cells derived from human neuroblastoma tissue with characteristics similar to neurons. Collectively, these results suggested that NMB restored erectile function via protection of the cavernous body from injury and stimulation of the survival of the associated nerves. NMB may be useful to treat ED patients with a severely damaged cavernous body.

No MeSH data available.


Related in: MedlinePlus