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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

Elastica van Gieson staining of the cavernous body isolated from age-matched positive control rats and STZ-induced diabetic rats injected with AdGFP or AdNMB.AdGFP (STZ/AdGFP) and AdNMB (STZ/AdNMB) were injected into the penises of STZ-induced diabetic rats and the penises were harvested for Elastica van Gieson staining 4 weeks later. Age-matched non-diabetic rats were used as positive controls (PC). (A) The histology of the root portion of penis (longitudinal section) is shown. Bars are 300 μm. (B) The histology of the cross section of penis is shown. Arrowheads indicate the dorsal penile nerves. Bars are 300 μm.
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pone.0133874.g004: Elastica van Gieson staining of the cavernous body isolated from age-matched positive control rats and STZ-induced diabetic rats injected with AdGFP or AdNMB.AdGFP (STZ/AdGFP) and AdNMB (STZ/AdNMB) were injected into the penises of STZ-induced diabetic rats and the penises were harvested for Elastica van Gieson staining 4 weeks later. Age-matched non-diabetic rats were used as positive controls (PC). (A) The histology of the root portion of penis (longitudinal section) is shown. Bars are 300 μm. (B) The histology of the cross section of penis is shown. Arrowheads indicate the dorsal penile nerves. Bars are 300 μm.

Mentions: Elastica van Gieson staining was performed to observe morphological changes. Trabeculae of the cavernous body decreased in size in STZ-induced diabetic rats injected with AdGFP compared with those in age-matched positive control rats (Fig 4A). When AdNMB was injected into the penis, the size of trabeculae increased compared with that in AdGFP-injected diabetic rats and remained similar to that in positive control rats. The morphology of dorsal penile nerve did not change remarkably among the groups (Fig 4B). An immunohistochemical analysis was subsequently performed. VE-Cad immunostaining was observed on the surface of trabeculae of the cavernous body even in STZ-induced diabetic rats injected with AdGFP (Fig 5A). SMA was also immunostained on the surface of the trabeculae in STZ-induced diabetic rats injected with AdGFP (Fig 5B). However, the SMA-positive area looked thinner than that observed in the age-matched positive control rats. The SMA-positive area became thicker in the AdNMB-injected diabetic rats than in the AdGFP-injected diabetic rats. Immunostaining for nNOS in the dorsal penile nerve was also analyzed, as it has been reported that nitric oxide (NO) released from nitrergic nerves [34], which express nNOS and release NO as a transmitter, play pivotal roles in the initiation of erection [35]. The level of immunostaining for nNOS was remarkably decreased in the AdGFP-injected diabetic rats as compared with the age-matched positive control rats (Fig 5C). AdNMB injection restored the nNOS immunostaining as compared with the AdGFP-injected diabetic rats.


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)

Elastica van Gieson staining of the cavernous body isolated from age-matched positive control rats and STZ-induced diabetic rats injected with AdGFP or AdNMB.AdGFP (STZ/AdGFP) and AdNMB (STZ/AdNMB) were injected into the penises of STZ-induced diabetic rats and the penises were harvested for Elastica van Gieson staining 4 weeks later. Age-matched non-diabetic rats were used as positive controls (PC). (A) The histology of the root portion of penis (longitudinal section) is shown. Bars are 300 μm. (B) The histology of the cross section of penis is shown. Arrowheads indicate the dorsal penile nerves. Bars are 300 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133874.g004: Elastica van Gieson staining of the cavernous body isolated from age-matched positive control rats and STZ-induced diabetic rats injected with AdGFP or AdNMB.AdGFP (STZ/AdGFP) and AdNMB (STZ/AdNMB) were injected into the penises of STZ-induced diabetic rats and the penises were harvested for Elastica van Gieson staining 4 weeks later. Age-matched non-diabetic rats were used as positive controls (PC). (A) The histology of the root portion of penis (longitudinal section) is shown. Bars are 300 μm. (B) The histology of the cross section of penis is shown. Arrowheads indicate the dorsal penile nerves. Bars are 300 μm.
Mentions: Elastica van Gieson staining was performed to observe morphological changes. Trabeculae of the cavernous body decreased in size in STZ-induced diabetic rats injected with AdGFP compared with those in age-matched positive control rats (Fig 4A). When AdNMB was injected into the penis, the size of trabeculae increased compared with that in AdGFP-injected diabetic rats and remained similar to that in positive control rats. The morphology of dorsal penile nerve did not change remarkably among the groups (Fig 4B). An immunohistochemical analysis was subsequently performed. VE-Cad immunostaining was observed on the surface of trabeculae of the cavernous body even in STZ-induced diabetic rats injected with AdGFP (Fig 5A). SMA was also immunostained on the surface of the trabeculae in STZ-induced diabetic rats injected with AdGFP (Fig 5B). However, the SMA-positive area looked thinner than that observed in the age-matched positive control rats. The SMA-positive area became thicker in the AdNMB-injected diabetic rats than in the AdGFP-injected diabetic rats. Immunostaining for nNOS in the dorsal penile nerve was also analyzed, as it has been reported that nitric oxide (NO) released from nitrergic nerves [34], which express nNOS and release NO as a transmitter, play pivotal roles in the initiation of erection [35]. The level of immunostaining for nNOS was remarkably decreased in the AdGFP-injected diabetic rats as compared with the age-matched positive control rats (Fig 5C). AdNMB injection restored the nNOS immunostaining as compared with the AdGFP-injected diabetic rats.

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