Short hairpin rna targeting insulin-like growth factor binding protein-3 restores the bioavailability of insulin-like growth factor-1 in diabetic rats

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Vol. 42 (1): 139-145, January – February, 2016

doi: 10.1590/S1677-5538.IBJU.2014.0416


ORIGINAL ARTICLE

Short hairpin rna targeting insulin-like growth factor binding protein-3 restores the bioavailability of insulin-like growth factor-1 in diabetic rats

Zhang-Yan Zhou 1, Guang-Jun Zhong 1, Shao-Ping Cheng 1, Hui Huang 1, Jing Wang 1, Hui Pan 1, Chang-Mao Liu 1, Cheng Xing 1, Ya-Ling Sun 1, Rong-Hua Liu 1, Fei-Li 1
1 Department of Urology, First Affiliated Hospital of Yangtze University, Jingzhou, HuBei, China


ABSTRACT

Purpose: To investigate whether intracavernosal injection of short hairpin RNA for IGFBP-3 could improve erectile function in streptozotocin-induced diabetic rats.
Materials and methods: After 12 weeks of IGFBP-3 short hairpin RNA injection treatment, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 and IGF-1 at mRNA and protein levels were detected by quantitative real-time PCR analysis and Western blot, respectively.
The concentration of cavernous cyclic guanosine monophosphate was detected by enzyme-linked immunosorbent assay.
Results: At 12 weeks after intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic group (P<0.05). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. At the same time, cavernous IGF-1 expression was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Cavernous cyclic guanosine monophosphate concentration was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01).
Conclusions: Gene transfer of IGFBP-3 shRNA could improve erectile function via the restoration of cavernous IGF-1 bioavailability and an increase of cavernous cGMP concentration in the pathogenesis of erectile dysfunction in streptozotocin-induced diabetic rats.

Keywords: Insulin-like growth factor binding protein-3; insulin-like growth factor-1; erectile dysfunction

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