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shRNA constructs targeting IGFBP-3 alleviate age related erectile dysfunction in the rat.

Authors: Pu, XY  Wen, AM  Liu, JM  Zheng, XG  Xiao, HJ  Xu, ZP  Wang, HP  Li, D  Zhang, RL 
Citation: Pu XY, etal., J Urol. 2014 Sep;192(3):990-6. doi: 10.1016/j.juro.2014.02.042. Epub 2014 Feb 24.
Pubmed: (View Article at PubMed) PMID:24576658
DOI: Full-text: DOI:10.1016/j.juro.2014.02.042

PURPOSE: We investigated whether injecting shRNA constructs targeting IGFBP-3 in the penis of old rats would improve erectile function. MATERIALS AND METHODS: The most validated IGFBP-3 shRNA plasmid vector (pGPU6/GFP/Neo-shIGFBP-3) was prepared and injected in penile corpus cavernosum tissue. A total of 30 old (age 24 months) male Sprague Dawley(R) rats were randomly divided into 3 groups, including 10 each that received phosphate buffered saline only (100 mul), pGPU6/GFP/Neo-shNC (100 mug) and the most validated plasmid constructs pGPU6/GFP/Neo-shIGFBP-3 (100 mug). At 4 weeks the erectile response was measured as intracavernous pressure. The percent of smooth muscle in corpus cavernosum tissue was evaluated. Nitric oxide synthase activity and the cGMP concentration in penile tissue were also analyzed. IGFBP-3 was estimated in penile tissue by Western blot, real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. RESULTS: pGPU6/GFP/Neo-shIGFBP-3 corrected the impaired erectile response in aged rats compared with the response in those injected with phosphate buffered saline and pGPU6/GFP/Neo-shNC (each p <0.01). The percent of cavernous smooth muscle was increased in the pGPU6/GFP/Neo-shIGFBP-3 group. Nitric oxide synthase activity and the cGMP concentration were also significantly increased in rats treated with pGPU6/GFP/Neo-shIGFBP-3. IGFBP-3 shRNA effectively reduced IGFBP-3 mRNA and protein expression in penile corpus cavernosum tissue. CONCLUSIONS: Decreasing IGFBP-3 expression by plasmid expressed shRNA improved erectile function in aged rats. The therapy may modulate smooth muscle integrity and increase the cGMP concentration. This may be a new direction for treating erectile dysfunction in clinical practice.


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CRRD Object Information
CRRD ID: 10402763
Created: 2015-10-28
Species: All species
Last Modified: 2015-10-28
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.