title: Short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 ameliorates diabetes mellitus-related erectile dysfunction in rats.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors: Zhonghua
authors: Z
authors: Yang
authors: Zhangyan
authors: Z
authors: Zhou
authors: Xinghuan
authors: X
authors: Wang
authors: Mou
authors: M
authors: Peng
authors: Haihong
authors: H
authors: Zhou
authors: Zhe
authors: Z
authors: Meng
authors: Dong
authors: D
authors: Chen
authors: Yongzhi
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006152:Cyclic GMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D008297:Male; D010413:Penis / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013311:Streptozocin
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013311:Streptozocin; D006152:Cyclic GMP