Login to Access Video or Poster Abstract: MP81-14
Sources of Funding: none

Introduction

Our previous studies have demonstrated that Human Tissue Kallikrein 1 (hKLK1) improved erectile function via several signaling pathways related to such as oxidative stress or corporal cavernosal fibrosis. However, the potential molecular mechanisms of hKLK1 inhibited age-related erectile dysfunction via modulating autophagy remains unknown. The aim of this article is to partly clarify the mechanisms of hKLK1 improving the erectile function in aged rats._x000D_

Methods

Male wild-type Sprague-Dawley rats (WTR) and transgenic rats expressing the hKLK1 gene (TGR) were fed to 4 and 18 months of age, respectively, and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR) and aged TGR (aTGR). Cavernous nerve electrostimulation was used to evaluate the erectile function of all rats. Transmission electron microscopy, immunohistochemistry, and western blotting were performed to determine the levels of autophagy. Related signaling pathways were detected by western blot and immunohistochemistry._x000D_

Results

Compared with the yWTR group and aTGR group, the aWTR group showed (1)lower erectile function: lower intracavernosal pressure(ICP)/mean arterial pressure(MAP) ratio; (2) reduced expressions of eNOS and nNOS, lower NO level; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) low expression levels of PI3K/Akt/mTOR and Hif-1?/Cox-2 pathways.

Conclusions

The hKLK1 gene played a potential role of restoring erectile function in aged transgenic rats through modulating autophagy via PI3K/Akt/mTOR and Hif-1?/Cox-2 pathways. This finding provided evidence for hKLK1 being gene therapy method of age-related erectile dysfunction. _x000D_

Funding

none