saRNA guided iNOS up-regulation improves erectile function of diabetic rats.

Abstract

PURPOSE:

Promoter targeted saRNAs mediate sequence specific up-regulation of gene expression. We explored the therapeutic effect of RNA activation mediated iNOS gene activation on improving erectile function in a rat model of diabetes mellitus.

MATERIALS AND METHODS:

An optimal saRNA sequence specific for iNOS promoter was cloned into an adenoviral vector, resulting in AdU6/shiNOS and AdU6/shControl. The corresponding viruses were used to transduce cultured rat cavernous smooth muscle cells. Streptozotocin induced diabetes models were established in rats and used to test the effects of intracavernous delivery of iNOS saRNA viruses on erectile function. iNOS expression in the cavernous smooth muscle cells or penile tissue of treated rats was assessed by reverse transcriptase-polymerase chain reaction and Western blot. Cyclic guanosine monophosphate was analyzed by enzyme-linked immunosorbent assay. Intracavernous pressure in response to cavernous nerve stimulation was measured using a data acquisition system on post-injection days 1, 3, 5, 7, 10 and 14.

RESULTS:

Adenovirus mediated expression of iNOS saRNA caused sustained up-regulation of iNOS in cavernous smooth muscle cells. Intracavernous injection of AdU6/shiNOS activated iNOS expression in vivo and significantly increased peak intracavernous pressure in streptozotocin induced diabetic rats via nitric oxide/intracellular cyclic guanosine monophosphate activation.

CONCLUSIONS:

Results show that saRNA mediated iNOS over expression in the penis can restore erectile function in streptozocin diabetic rats via the nitric oxide-cyclic guanosine monophosphate pathway.

• Authors: Tao Wang, Mingchao Li, Huixin Yuan, Yin Zhan, Hua Xu, Shaogang Wang, Weiming Yang, Jihong Liu, Zhangqun Ye, Long-Cheng Li
• Journal: The Journal of urology (J Urol) Vol. 190 Issue 2 Pg. 790-8 (Aug 2013) ISSN: 1527-3792 [Electronic] United States
• PMID: 23523927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• RNA
• Nitric Oxide Synthase Type II
• Cyclic GMP

Topics

• Adenoviridae
• Analysis of Variance
• Animals
• Blotting, Western
• Cells, Cultured
• Cyclic GMP (physiology)
• Diabetes Mellitus, Experimental
• Enzyme-Linked Immunosorbent Assay
• Male
• Muscle, Smooth (physiology)
• Nitric Oxide Synthase Type II (metabolism)
• Penile Erection (physiology)
• RNA (pharmacology)
• Rats
• Real-Time Polymerase Chain Reaction
• Sequence Analysis, RNA
• Signal Transduction
• Up-Regulation