The role of hedgehog-interacting protein in maintaining cavernous nerve integrity and adult penile morphology.
The role of hedgehog-interacting protein in maintaining cavernous nerve integrity and adult penile morphology.
复制标题
DOI：
10.1111/j.1743-6109.2009.01349.x
复制
发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Podlasek CA
中科院分区：
文献类型：
--
作者：
Angeloni NL;Bond CW;Monsivais D;Tang Y;Podlasek CA
Sonic hedgehog（SHH）是阴茎平滑肌细胞凋亡的重要调节因子，其作为抑制阴茎切除术后细胞凋亡的疗法具有显著的临床潜力，细胞凋亡是勃起功能障碍（艾德）的潜在原因。因此，了解SHH信号在成年阴茎中的调节方式对于推动艾德研究领域的发展和开发新的治疗策略至关重要。我们建议，刺猬相互作用蛋白（HIP），已被证明结合SHH蛋白，并发挥作用，在SHH调节胚胎发育过程中的其他器官，是一个重要的调节SHH信号，阴茎形态，和细胞凋亡诱导。我们检测了在出生后阴茎分化、CN损伤和糖尿病ED模型中阴茎和海绵体神经（CN）中的HIP信号传导。在7至92日龄的Sprague-Dawley大鼠中，通过免疫组织化学（IHC）分析和实时逆转录酶-聚合酶链反应（RT-PCR）检测HIP定位/丰度和RNA丰度，在CN损伤的Sprague-Dawley大鼠和BioBreeding/Worcester糖尿病大鼠中。HIP信号在骨盆神经节和阴茎中受到干扰，并在阴茎中进行TUNEL测定。进行CN连接、利多卡因和抗驱动蛋白实验以检查CN和阴茎中的HIP信号传导。在这项研究中，我们是第一个证明，HIP通过CN进行顺行运输到阴茎，HIP扰动骨盆神经节或阴茎诱导细胞凋亡，HIP在维持CN的完整性，阴茎形态和SHH丰度中发挥作用。这些研究是重要的，因为它们显示HIP参与骨盆神经节和阴茎之间的串扰（信号传导），这对于维持阴茎形态是不可或缺的，并且它们提出了神经如何调节靶器官形态和功能的机制。
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. 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. 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. 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. 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.
登录
查看更多内容
影响因子：
6.6
作者：
Klein, LT;Miller, MI;Shabsigh, R
通讯作者：
Shabsigh, R
影响因子：
6.6
作者：
Johannes, CB;Araujo, AB;McKinlay, JB
通讯作者：
McKinlay, JB
影响因子：
1.7
作者：
Loulier, K;Ruat, M;Traiffort, E
通讯作者：
Traiffort, E
影响因子：
3.6
作者：
Bond, Christopher;Tang, Yi;Podlasek, Carol A.
通讯作者：
Podlasek, Carol A.
影响因子：
3.5
作者：
Heruti, Rafi;Shochat, Tzipi;Justo, Dan
通讯作者：
Justo, Dan