PMID- 17097800 OWN - NLM STAT- MEDLINE DCOM- 20070927 LR - 20220321 IS - 0302-2838 (Print) IS - 0302-2838 (Linking) VI - 52 IP - 2 DP - 2007 Aug TI - Upregulation of penile brain-derived neurotrophic factor (BDNF) and activation of the JAK/STAT signalling pathway in the major pelvic ganglion of the rat after cavernous nerve transection. PG - 574-80 AB - OBJECTIVES: Increasing attention is being focused on identifying novel approaches to recover cavernous nerve (CN) function after injury or secondary to disease states such as diabetes mellitus. We examined penile brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) expression, and activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) molecular pathway in the major pelvic ganglion (MPG) after CN injury in the rat. METHODS: Five groups of eight male Sprague-Dawley rats (4 mo, 250-300 g) were used in this study. The penis and MPG with attached CN segment were harvested at 0 h (controls), 12, and 24 h, as well as at 5 and 12 d after CN axotomy, for protein, messenger RNA (mRNA), and immunohistochemical analysis. RESULTS: mRNA and protein expression of BDNF was upregulated in the penis after injury (p<0.05). Levels of NT-3 were unchanged. The JAK/STAT pathway was activated in the MPG after transection, as evidenced by increased STAT1 (peak: 24 h) and STAT3 (peak: 5 d) phosphorylation (p<0.01 vs. controls). CONCLUSIONS: This study demonstrates increased expression of penile BDNF and upregulation of phosphorylated STAT1 and STAT3 in the MPG in response to CN transection. Activation of the JAK/STAT pathway after injury represents a promising new molecular target for modulating CN survival and regeneration. FAU - Bella, Anthony J AU - Bella AJ AD - Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA 94143-0738, USA. abella@urology.ucsf.edu FAU - Lin, Guiting AU - Lin G FAU - Garcia, Maurice M AU - Garcia MM FAU - Tantiwongse, Kavirach AU - Tantiwongse K FAU - Brant, William O AU - Brant WO FAU - Lin, Ching-Shwun AU - Lin CS FAU - Lue, Tom F AU - Lue TF LA - eng GR - R37-DK-45370/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20061030 PL - Switzerland TA - Eur Urol JT - European urology JID - 7512719 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (STAT Transcription Factors) RN - EC 2.7.10.2 (Jak1 protein, rat) RN - EC 2.7.10.2 (Janus Kinase 1) RN - EC 2.7.10.2 (Janus Kinases) SB - IM CIN - Eur Urol. 2007 Aug;52(2):580-1. PMID: 17674438 MH - Analysis of Variance MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Ganglia, Parasympathetic/*metabolism MH - Immunoenzyme Techniques MH - Janus Kinase 1 MH - Janus Kinases/*metabolism MH - Male MH - Penis/*innervation/*metabolism/surgery MH - Rats MH - Rats, Sprague-Dawley MH - STAT Transcription Factors/*metabolism MH - Signal Transduction MH - Up-Regulation EDAT- 2006/11/14 09:00 MHDA- 2007/09/28 09:00 CRDT- 2006/11/14 09:00 PHST- 2006/07/26 00:00 [received] PHST- 2006/10/18 00:00 [accepted] PHST- 2006/11/14 09:00 [pubmed] PHST- 2007/09/28 09:00 [medline] PHST- 2006/11/14 09:00 [entrez] AID - S0302-2838(06)01334-0 [pii] AID - 10.1016/j.eururo.2006.10.043 [doi] PST - ppublish SO - Eur Urol. 2007 Aug;52(2):574-80. doi: 10.1016/j.eururo.2006.10.043. Epub 2006 Oct 30.