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Maintenance of the contractile phenotype in corpus cavernosum smooth muscle cells by Myocardin gene therapy ameliorates erectile dysfunction in bilateral cavernous nerve injury rats.
- Source :
-
Andrology [Andrology] 2017 Jul; Vol. 5 (4), pp. 798-806. Date of Electronic Publication: 2017 May 23. - Publication Year :
- 2017
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Abstract
- The pathophysiology of erectile dysfunction post radical prostatectomy is not clearly clarified, and the low efficacy of traditional PDE5i treatment remains a major complaint in contemporary practice. This study aimed to demonstrate phenotypic modulation in bilateral cavernous nerve injury (BCNI) rats within 7 days, and subsequently validate gene therapy with Myocardin (Mycod) by maintaining a contractile phenotype in corpus cavernosum smooth muscle cells. Initially, 36 male rats were randomly divided into BCNI and negative control (NC) groups for histological and phenotypic molecular measurements at 3, 5, and 7 days. Afterwards, an additional 30 rats received a single intra-cavernous injection of 50 μL PBS, Ad-Myocd (1 × 10 <superscript>11</superscript>  pfu/ml) or Ad-vector for 10 animals each, namely the NC+PBS, BCNI+Ad-Myocd, and BCNI+Ad-vector groups. Finally, the validity and mechanism of Myocd transfection was explored at 21 days in vivo and 48 h in vitro. Western blotting showed canonical declines in Myocd, α-SMA, and Calponin expression, as well as elevated Osteopontin (OPN) expression, before corporeal morphological and SM-to-collagen ratio changes at day 5 after injury. Overexpression of Myocd maintained the contractile phenotype of corpus cavernosum smooth muscle cells, ameliorated bilateral cavernous nerve injury rat erectile dysfunction, as well as promoted cell contractility and suppressed proliferative capacity. Simultaneously, confocal imaging revealed up-regulation and co-localization of serum response factor in gene-transferred cells. In conclusion, our study is the first to investigate corpus cavernosum smooth muscle cells phenotypes in the early stages of cavernous injury model rats, and Myocd reversed phenotypic modulation by activating serum response factor. The experimental results demonstrated the validity of gene therapy for erectile dysfunction.<br /> (© 2017 American Society of Andrology and European Academy of Andrology.)
- Subjects :
- Actins metabolism
Animals
Calcium-Binding Proteins metabolism
Cells, Cultured
Disease Models, Animal
Erectile Dysfunction genetics
Erectile Dysfunction metabolism
Erectile Dysfunction physiopathology
Male
Microfilament Proteins metabolism
Muscle, Smooth metabolism
Nuclear Proteins genetics
Osteopontin metabolism
Penis metabolism
Phenotype
Rats, Sprague-Dawley
Time Factors
Trans-Activators genetics
Calponins
Erectile Dysfunction therapy
Genetic Therapy methods
Muscle Contraction
Muscle, Smooth innervation
Myocytes, Smooth Muscle metabolism
Nerve Crush
Nuclear Proteins biosynthesis
Penile Erection
Penis innervation
Trans-Activators biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 2047-2927
- Volume :
- 5
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Andrology
- Publication Type :
- Academic Journal
- Accession number :
- 28544569
- Full Text :
- https://doi.org/10.1111/andr.12375