Cavernous smooth muscles: innovative potential therapies are promising for an unrevealed clinical diagnosis

Hassanin, Ahmed Mohamed; Abdel-Hamid, Ahmed Zain

doi:10.1007/s11255-019-02309-9

Cited by 9 publications

(10 citation statements)

References 95 publications

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“…Erectile function is regulated by the diastolic and contractile functions of corpus cavernous smooth muscle cells (CCSMCs). After the loss of innervation of the cavernous body in patients with CNI-ED, CCSMCs gradually deteriorate, mainly manifested as increased intracellular muscle protein degradation, significantly reduced muscle content, inhibited cell proliferation, and apoptosis [ 25–27 ], which eventually leads to ED.…”

Section: Discussionmentioning

confidence: 99%

Whole-transcriptome analysis of rat cavernosum and identification of circRNA-miRNA-mRNA networks to investigate nerve injury erectile dysfunction pathogenesis

Huang

Wang

et al. 2021

Bioengineered

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There is growing evidence that circular RNAs (circRNAs) play a vital role in many kinds of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover novel circRNAs, probed their potential role in the CNI-ED, and construct a ceRNA network of circRNAs. Twelve male Sprague Dawley rats were randomly divided into 2 groups by us: bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for RT-qPCR. CeRNA network of circRNAs was established using Cytoscape. GO and KEGG analysis was done by R package. Sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR.The ceRNA network contained ten circRNAs, six miRNAs, and 227 mRNAs, including 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs. GO and KEGG analysis suggested that these ten circRNAs could main regulate energy metabolism processes. A protein-protein interaction network was constructed with the mRNAs in ceRNA network, and five hub genes were identified. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.

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Section: Discussionmentioning

confidence: 99%

Whole-transcriptome analysis of rat cavernosum and identification of circRNA-miRNA-mRNA networks to investigate nerve injury erectile dysfunction pathogenesis

Huang

Wang

et al. 2021

Bioengineered

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“…Also, the time intervals of taking penile samples for these purposes vary depending on the CF model because of different dynamics of fibrogenesis caused by pathology in NO-cGMP, TGF-β, SHH, VEGF, and ROCK signaling pathways. 6 For instance, while CF occurs rapidly following cavernous nerve injury and castration within 2-4 weeks, 7,8 in diabetes mellitus, similar morphological changes can be observed within 6-12 weeks, 9,10 and in aging signs of CF could be detected throughout the entire life of laboratory animals. 11 One of the perspective diagnostic methods for CF is microcomputed tomography (micro-CT).…”

Section: Introductionmentioning

confidence: 96%

“…The only available method of penile visualization in rats is the histopathological analysis due to the relatively small penis size of the laboratory animals. Also, the time intervals of taking penile samples for these purposes vary depending on the CF model because of different dynamics of fibrogenesis caused by pathology in NO‐cGMP, TGF‐β, SHH, VEGF, and ROCK signaling pathways 6 . For instance, while CF occurs rapidly following cavernous nerve injury and castration within 2–4 weeks, 7,8 in diabetes mellitus, similar morphological changes can be observed within 6–12 weeks, 9,10 and in aging signs of CF could be detected throughout the entire life of laboratory animals 11 …”

Section: Introductionmentioning

confidence: 99%

X‐ray micro‐computed tomography in the assessment of penile cavernous fibrosis in a rabbit castration model

et al. 2021

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Background: Current assessment methods of penile cavernous fibrosis in animal models have limitations due to the inability to provide complex and volume analysis of fibrotic alterations. Objective:The aim was to evaluate micro-computed tomography for assessment of cavernous fibrosis and compare it with histological, histochemical, immunohistochemical, and RT-PCR analysis. Materials and methods:A controlled trial was performed involving 25 New Zealand male rabbits with induced testosterone deficiency by orchidectomy. Penile samples were obtained before and after 7, 14, 21, and 84 days from orchidectomy. We consistently performed (a) gray value analysis of corpora cavernosa 3D models reconstructed after micro-computed tomography, (b) morphometry of smooth muscles/connective tissue ratio, collagen type I/III ratio, and area of TGF-beta-1 expression in corpora cavernosa, and (c) RT-PCR of TGF-beta-1 expression.Results: Micro-computed tomography allowed visualization of penile structures at a resolution comparable to light microscopy. Gray values of corpora cavernosa decreased from 1673 (1512-1773) on the initial day to 1184 (1089-1232) on the 21st day (p < 0.005). However, on the 84th day, it increased to 1610 (1551-1768). On 21st and 84th days, there was observed a significant decrease in smooth muscle/connective tissue ratio and a significant increase in collagen type I/III ratio (p < 0.05). TGF-beta1 expression increased on the 84th day according to immunohistochemistry (p < 0.005).RT-PCR was impossible to conduct due to the absence of RNA in obtained samples after micro-CT.Discussion and conclusions: Micro-computed tomography provided 3D visualization of entire corpora cavernosa and assessment of radiodensity alterations by gray value

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“…Presently, phosphodiesterase type V inhibitors are the first choice of oral drugs for the treatment of ED in the clinic. However, the efficacy of these for CN‐injured ED is not clear and the therapeutic strategy is also still under investigation (Fode et al., 2019; Hassanin & Abdel‐Hamid, 2020). In addition, second‐ and third‐line treatments, such as the intracavernosal injection of vasoactive substances, vacuum erection devices and penile prosthesis implantation, have caused unavoidable traumatic damage to the penis (Chung & Gillman, 2014; Polito et al., 2012; Ramsawh et al., 2005).…”

Section: Introductionmentioning

confidence: 99%

Enhanced effects of salidroside on erectile function and corpora cavernosa autophagy in a cavernous nerve injury rat model

Zhao

et al. 2021

Andrologia

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We explored the efficacy and mechanisms of salidroside treatment for erectile dysfunction induced by bilateral cavernous nerve injury (BCNI). Forty male rats were divided into four groups as follows: sham (cavernous nerves exposed only) (S); BCNI (M); BCNI + rapamycin (M + rapamycin); and BCNI + salidroside (M + salidroside). Erectile function in the rats was measured by intracavernosal pressure. Penile tissue was harvested for transmission electron microscopy, immunohistochemistry, immunofluorescence, Masson's trichrome staining, haematoxylin–eosin staining, TdT‐mediated dUTP Nick End Labeling and western blotting. The M group exhibited a decrease in erectile responses and increased apoptosis and fibrosis compared to these in the S group. Meanwhile, nerve content and the penile atrophy index were also decreased in the M group. Treatment with salidroside and rapamycin for 3 weeks partially restored erectile function and significantly attenuated corporal apoptosis, fibrosis, nerve content and penile atrophy in the M group. Moreover, the autophagy level was further enhanced in the M + salidroside group, which was the same as that in the positive observation group (M + rapamycin). Salidroside treatment not only improved erectile function in rats with BCNI, but also inhibited apoptosis and fibrosis and ameliorated the loss of nerve content and endothelial and corpus cavernosum smooth muscle cells by promoting protective autophagy.

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Cavernous smooth muscles: innovative potential therapies are promising for an unrevealed clinical diagnosis

Cited by 9 publications

References 95 publications

Whole-transcriptome analysis of rat cavernosum and identification of circRNA-miRNA-mRNA networks to investigate nerve injury erectile dysfunction pathogenesis

Whole-transcriptome analysis of rat cavernosum and identification of circRNA-miRNA-mRNA networks to investigate nerve injury erectile dysfunction pathogenesis

X‐ray micro‐computed tomography in the assessment of penile cavernous fibrosis in a rabbit castration model

Enhanced effects of salidroside on erectile function and corpora cavernosa autophagy in a cavernous nerve injury rat model

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