hedgehog 相互作用蛋白在维持海绵体神经完整性和成年阴茎形态中的作用。
The role of hedgehog-interacting protein in maintaining cavernous nerve integrity and adult penile morphology.
机构信息
Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA.
出版信息
J Sex Med. 2009 Sep;6(9):2480-93. doi: 10.1111/j.1743-6109.2009.01349.x. Epub 2009 Jun 9.
INTRODUCTION
Sonic hedgehog (SHH) is an essential regulator of smooth muscle apoptosis in the penis that has significant clinical potential as a therapy to suppress post-prostatectomy apoptosis, an underlying cause of erectile dysfunction (ED). Thus an understanding of how SHH signaling is regulated in the adult penis is essential to move the field of ED research forward and to develop new treatment strategies. We propose that hedgehog-interacting protein (HIP), which has been shown to bind SHH protein and to play a role in SHH regulation during embryogenesis of other organs, is a critical regulator of SHH signaling, penile morphology, and apoptosis induction.
AIMS
We have examined HIP signaling in the penis and cavernous nerve (CN) during postnatal differentiation of the penis, in CN-injured, and a diabetic model of ED.
METHODS
HIP localization/abundance and RNA abundance were examined by immunohistochemical (IHC) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in Sprague-Dawley rats between the ages of 7 and 92 days old, in CN-injured Sprague-Dawley rats and in BioBreeding/Worcester diabetic rats. HIP signaling was perturbed in the pelvic ganglia and in the penis and TUNEL assay was performed in the penis. CN tie, lidocaine, and anti-kinesin experiments were performed to examine HIP signaling in the CN and penis.
RESULTS
In this study we are the first to demonstrate that HIP undergoes anterograde transport to the penis via the CN, that HIP perturbation in the pelvic ganglia or the penis induces apoptosis, and that HIP plays a role in maintaining CN integrity, penile morphology, and SHH abundance.
CONCLUSIONS
These studies are significant because they show HIP involvement in cross-talk (signaling) between the pelvic ganglia and penis, which is integral for maintenance of penile morphology and they suggest a mechanism of how nerves may regulate target organ morphology and function.
简介
Sonic hedgehog（SHH）是阴茎平滑肌细胞凋亡的重要调节因子，具有抑制前列腺切除术后凋亡的显著临床潜力，而凋亡是勃起功能障碍（ED）的根本原因。因此，了解 SHH 信号在成年阴茎中的调控机制对于推动 ED 研究领域的发展和开发新的治疗策略至关重要。我们提出， hedgehog-interacting protein（HIP）已被证明可以与 SHH 蛋白结合，并在其他器官的胚胎发生过程中发挥调节 SHH 的作用，是 SHH 信号、阴茎形态和凋亡诱导的关键调节因子。
目的
我们研究了 HIP 在阴茎和海绵体神经（CN）在阴茎出生后分化过程中的信号，以及在 CN 损伤和糖尿病 ED 模型中的信号。
方法
通过免疫组织化学（IHC）分析和实时逆转录聚合酶链反应（RT-PCR），在 7 至 92 天大的 Sprague-Dawley 大鼠中，在 CN 损伤的 Sprague-Dawley 大鼠和 BioBreeding/Worcester 糖尿病大鼠中，研究了 HIP 定位/丰度和 RNA 丰度。在阴茎中进行 HIP 信号干扰和 TUNEL 检测。进行 CN 结扎、利多卡因和抗动力蛋白实验，以研究 CN 和阴茎中的 HIP 信号。
结果
在这项研究中，我们首次证明 HIP 通过 CN 逆行运输到阴茎，HIP 在盆腔神经节或阴茎中的干扰会诱导细胞凋亡，并且 HIP 在维持 CN 完整性、阴茎形态和 SHH 丰度方面发挥作用。
结论
这些研究意义重大，因为它们表明 HIP 参与了盆腔神经节和阴茎之间的串扰（信号），这对于维持阴茎形态至关重要，并且它们提出了神经如何调节靶器官形态和功能的机制。
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