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
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
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DOI：
10.1016/j.eururo.2006.10.043
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发表时间：
2007-08-01
期刊：
影响因子：
23.4
通讯作者：
Lue, Tom F.
中科院分区：
文献类型：
--
作者：
Bella, Anthony J.;Lin, Guiting;Lue, Tom F.
目的：越来越多的人关注于寻找新的方法来恢复损伤后或继发于糖尿病等疾病状态的海绵体神经(CN)功能。我们检测了大鼠CN损伤后阴茎脑源性神经营养因子(BDNF)和神经营养素-3(NT-3)的表达，以及Janus激酶(JAK)/信号转导和转录激活因子(STAT)分子通路的激活。分别于伤后0 h(对照组)、12 h、24 h、5 d、12 d、12 d取阴茎及附着性CN节段的MPG，进行蛋白质、信使RNA(MRNA)及免疫组织化学分析。结果：阴茎损伤后BDNFmRNA和蛋白表达上调(p<；0.05)。NT-3水平无明显变化。切断后，MPG的JAK/STAT通路被激活，STAT1(峰值：24 h)和STAT3(峰值：5 d)磷酸化水平(p<；0.01与对照组相比增加)。结论：本研究证实了阴茎BDNF的表达增加和磷酸化的STAT1和STAT3在MPG的上调。损伤后JAK/STAT通路的激活是调控CN存活和再生的一个有希望的新分子靶点。(C)2006年欧洲泌尿外科协会。爱思唯尔出版，版权所有。
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. (C) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.