Short Hairpin Ribonucleic Acid Constructs Targeting Insulin-like Growth Factor Binding Protein-3 Ameliorates Diabetes Mellitus-related Erectile Dysfunction in Rats - 31/01/13
, Mou Peng a, Haihong Zhou a, Zhe Meng a, Dong Chen a, Yongzhi Wang a
Reprint requests: Xinghuan Wang, M.D., Ph.D., Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071 China.Abstract |
Objective |
To investigate the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in penile cavernous of streptozotocin (STZ)-induced DM rats and whether downregulation of IGFBP-3 by intracavernosal injection of short hairpin ribonucleic acid (shRNA) targeting IGFBP-3 could improve the erectile function in DM rats.
Materials and Methods |
Diabetes was induced in rats by intraperitoneal injection of STZ, and the expression of IGFBP-3 in the penile tissue of adult normal and DM male rats was assayed using reverse transcriptase-polymerase chain reaction and Western blot. Next, shRNA-targeting IGFBP-3 and a scramble sequence were injected into the penile corpora cavernosa of DM rats. At 12 weeks after shRNA-IGFBP-3 administration, the intracavernous pressure in response to electrical stimulation of the cavernous nerves was evaluated. The expression of IGFBP-3 was assayed by Western blot. The concentration of cyclic guanosine monophosphate in the corpus cavernosum was assayed by enzyme-linked immunosorbent assay.
Results |
At 12 week after intraperitoneal administration of STZ, IGFBP-3 expression had increased in the penis of the DM rat (P <.05) compared with that of the normal control rats. Among the DM rats, IGFBP-3 expression at the messenger RNA and protein level was significantly inhibited 12 weeks after intracavernous administration of IGFBP-3 shRNA (P <.01). At 12 weeks after shRNA-IGFBP-3 injection, intracavernosal pressure was significantly increased in response to cavernous nerve stimulation (P <.05), and an increase in the concentration of cyclic guanosine monophosphate in the corpus cavernous tissue (P <.01) was detected compared with the “randomer” shRNA treatment group.
Conclusion |
Gene transfer of shRNA-IGFBP-3 could improve erectile function in STZ-induced DM rats by an increase in the cyclic guanosine monophosphate concentration in cavernous tissue.
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| Z. Yang and Z. Zhou contributed to this study equally. |
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| Financial Disclosure: The authors declare that they have no relevant financial interests. |
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| Funding Support: This study was supported by the National Natural Science Foundation of China (grant 81172734) and Independent Research Projects of Wuhan University (grant 111086). |
Vol 81 - N° 2
P. 464.e11-464.e16 - febbraio 2013 Ritorno al numero
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