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Clin Sci (Lond). 2018 Oct 18;132(20):2175-2188. doi: 10.1042/CS20180192. Print 2018 Oct 31.

Decreased expression of pigment epithelium-derived factor within the penile tissues contributes to erectile dysfunction in diabetic rats.

Author information

1
Department of Physiology, Shantou University Medical College, Shantou 515041, China.
2
Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, U.S.A.
3
Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China.
4
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, U.S.A.
5
Department of Physiology, Shantou University Medical College, Shantou 515041, China dnqin@stu.edu.cn.

Abstract

Increased production of reactive oxygen species (ROS) and inflammation are major contributors to the development and progression of diabetes-associated erectile dysfunction (DMED). As an endogenous antioxidant and anti-inflammatory factor, the potential implication of pigment epithelium-derived factor (PEDF) in DMED has not been revealed. To assess the potential antioxidant and anti-inflammatory functions of PEDF in DMED, we first demonstrated that PEDF was significantly decreased at the levels of the mRNA and protein in the penis of diabetic rats compared with normal controls. To test the hypothesis that decreased the penile levels of PEDF are associated with oxidative stress and inflammation in DMED, an adenovirus expressing PEDF (Ad-PEDF) or the same titer of control virus (Ad-GFP) was intracavernously administered at 2 weeks after diabetic onset. After 6 weeks of treatment, we found that administration of Ad-PEDF could significantly increase erectile response to cavernosal nerve stimulation in the diabetic rats by restoring the endothelial NO synthase (eNOS), P-eNOS, and neuronal NO synthase (nNOS) protein levels to the standard levels represented in normal rats and by suppressing the levels of tumor necrosis factor-α (TNF-α) and oxidative stress. In conclusion, the present data indicated that the antioxidant and anti-inflammatory potential of PEDF plays important role in restoring erectile function by the inhibition of oxidative stress and TNF-α production.

KEYWORDS:

Oxidative Stress; TNF-α; diabetes-associated erectile dysfunction; inflammation; pigment epithelium-derived factor

PMID:
30232174
DOI:
10.1042/CS20180192

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