Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.
Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.
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DOI：
10.1186/s12964-021-00755-6
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发表时间：
2021-07-20
期刊：
影响因子：
--
通讯作者：
Kyprianou N
中科院分区：
文献类型：
--
作者：
Archer M;Dogra N;Dovey Z;Ganta T;Jang HS;Khusid JA;Lantz A;Mihalopoulos M;Stockert JA;Zahalka A;Björnebo L;Gaglani S;Noh MR;Kaplan SA;Mehrazin R;Badani KK;Wiklund P;Tsao K;Lundon DJ;Mohamed N;Lucien F;Padanilam B;Gupta M;Tewari AK;Kyprianou N
泌尿道高度受自主神经支配，自主神经在泌尿道发育、生长因子的产生和体内平衡的控制中是必不可少的。这些神经信号可能在良性和恶性的几种泌尿生殖系统（GU）疾病状态中失调。因此，自主神经系统是包括癌症、排尿功能障碍和阻塞性肾结石在内的几种泌尿生殖系统疾病的治疗靶点。肾上腺素能受体（肾上腺素受体）是分布在全身的G蛋白偶联受体。α1-肾上腺素受体的主要功能是通过GPCR和细胞内钙内流来传递平滑肌收缩信号。通过使用α-肾上腺素受体拮抗剂，α-和β-肾上腺素受体的药物干预在良性泌尿系统疾病的治疗中常规且成功地实施。此外，基于细胞的证据最近确定了α1-肾上腺素受体拮抗剂在前列腺、膀胱和肾肿瘤中的抗肿瘤作用，其通过调节表型上皮-间质转化（EMT）减少肿瘤微环境中的新生血管和损害生长。人们一直关注于将常规使用的、美国食品药品监督管理局批准的α1-肾上腺素受体拮抗剂重新用于抑制晚期前列腺癌、膀胱癌和肾癌患者的GU肿瘤生长和血管生成。在这篇综述中，我们讨论了以下方面的当前证据：（a）由其同源α-和β-肾上腺素受体介导的自主神经系统信号传导事件，调节泌尿生殖器官的表型景观（EMT）;和（b）靶向该信号传导途径的治疗意义良性和恶性泌尿系统疾病。B。视频摘要在线版本包含补充材料，可在10. 1186/s12964-021-00755-6。
The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract The online version contains supplementary material available at 10.1186/s12964-021-00755-6.
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影响因子：
2.8
作者：
Calmasini, Fabiano B.;Candido, Tuany Z.;Monica, Fabiola Z.
通讯作者：
Monica, Fabiola Z.
影响因子：
4.7
作者：
Braadland PR;Ramberg H;Grytli HH;Taskén KA
通讯作者：
Taskén KA
影响因子：
45.3
作者：
Barron, Thomas I.;Connolly, Roisin M.;Visvanathan, Kala
通讯作者：
Visvanathan, Kala
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
64.8
作者：
通讯作者：
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