Login to Access Video or Poster Abstract: MP45-17
Sources of Funding: The National Natural Science Foundation of China, 81571433, the Natural Science Foundation of Guangdong Province, China, 2014A030313302, and the Natural Science Foundation of Guangdong Province, China, 2015A030310075.

Introduction

The pathophysiology of erectile dysfunction (ED) following radical prostatectomy (RP) was not clearly clarified, and the low efficacy of the major PDE5i treatment remained a frequent complain clinically. This study aimed to demonstrate phenotypic modulation in bilateral cavernous nerve injury (BCNI) rats within 7 days, subsequently verify Myocardin gene therapy to maintain the contractile phenotype of corpus cavernosum smooth muscle cells (CCSMCs).

Methods

For the first part, 36 male rats were randomly assigned to BCNI and NC groups for histological and molecular measurements at 3, 5, 7 days. Afterwards, a single intracavernosal injection of 50uL PBS, Ad-Myocd (1x10^11 pfu/ml) or Ad-vector was given to three treatment groups with 10 animals each, defined as NC+PBS, BCNI+Ad-Myocd, BCNI+vector, at the day of molecular changing day found previously. Finally, the validity and mechanism of Myocardin transfection was explored in vivo and in vitro.

Results

Western blotting revealed canonical declined Myocd, a-SMA, Calponin and elevated OPN expression before corporeal SM-to-collagen ratio and morphological changes at 5th day after modeling. Overexpression of Myocardin maintained the contractile phenotype of CCSMCs, improved BCNI rat intracavernous pressures, as well as suppressed cell proliferative capacity and promoted contractility. In addition, confocal test showed up-regulation and co-localization of serum response factor (SRF) in gene-transfer cells.

Conclusions

In conclusion, our study was the first to investigate CCSM cell phenotypic switch in the early stage of BCNI rats, and Myocardin was capable of reversing phenotypic modulation by activating SRF. The experimental results validated the efficiency of gene therapy in erectile dysfunction.

Funding

The National Natural Science Foundation of China, 81571433, the Natural Science Foundation of Guangdong Province, China, 2014A030313302, and the Natural Science Foundation of Guangdong Province, China, 2015A030310075.