Role of metabolic ghrelin hormones for smooth muscle contraction and growth in benign prostatic hyperplasia

代谢性生长素释放肽激素对良性前列腺增生平滑肌收缩和生长的作用

• 批准号: 410334201
• 负责人: Professor Dr. Christian Gratzke
• 金额: --
• 依托单位: Urologische Klinik und Poliklinik (Campus Großhadern)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/410334201?language=en
• 关键词: Role; metabolic; ghrelin; hormones; smooth

In benign prostatic hyperplasia (BPH), increased prostate smooth muscle tone and prostate enlargement may promote bladder outlet obstruction and lower urinary tract symptoms (LUTS). The prevalence of such voiding symptoms is strikingly high. Smooth muscle tone and hyperplastic growth in the prostate are important targets for medical therapy of LUTS suggestive of BPH. However, the efficacy of available medications is insufficient, so that new options may be appreciated. The metabolic syndrome represents an important risk factor for LUTS in patients with BPH. Although this link has now been established based on epidemiological studies, underlying molecular mechanisms connecting LUTS/BPH with metabolic syndrome are still poorly understood. Previous studies dedicated to such mechanisms were rare, and focussed on inflammatory mediators or lipoproteins. However, metabolism and obesity may be driven by metabolic hormones, including ghrelin and its receptor (ghrelin/growth hormone secretagogue receptor, GHSR). Here, we propose investigations addressing the possible role of ghrelin and GHSR for regulation of prostate smooth muscle tone and prostate growth, including in vivo investigations in a rodent model of BPH.

在良性前列腺增生症(BPH)中，前列腺平滑肌张力增加和前列腺增大可促进膀胱出口梗阻和下尿路症状(LUTS)。这种排尿症状的患病率高得惊人。前列腺的平滑肌张力和增生是内科治疗前列腺增生症的重要靶点。然而，现有药物的疗效还不够，因此新的选择可能会受到重视。代谢综合征是BPH患者发生下尿路感染的重要危险因素。尽管这种联系现在已经建立在流行病学研究的基础上，但LUTS/BPH与代谢综合征之间的潜在分子机制仍然知之甚少。以前致力于这类机制的研究很少，主要集中在炎症介质或脂蛋白上。然而，代谢和肥胖可能是由代谢激素驱动的，包括Ghrelin及其受体(Ghrelin/生长激素促分泌素受体，GHSR)。在这里，我们建议进行研究，探讨Ghrelin和GHSR在调节前列腺平滑肌张力和前列腺生长中的可能作用，包括在BPH啮齿动物模型中的体内研究。

项目成果

The STK16 inhibitor STK16-IN-1 inhibits non-adrenergic and non-neurogenic smooth muscle contractions in the human prostate and the human male detrusor

• DOI: 10.1007/s00210-019-01797-x
• 发表时间: 2020-05-01
• 期刊: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
• 影响因子: 3.6
• 作者: Li, Bingsheng;Wang, Xiaolong;Hennenberg, Martin
• 通讯作者: Hennenberg, Martin

Ghrelin Aggravates Prostate Enlargement in Rats with Testosterone-Induced Benign Prostatic Hyperplasia, Stromal Cell Proliferation, and Smooth Muscle Contraction in Human Prostate Tissues

• DOI: 10.1155/2019/4748312
• 发表时间: 2019-11
• 期刊: Oxidative Medicine and Cellular Longevity
• 作者: Xiaolong Wang;Yiming Wang;C. Gratzke;C. Sterr;Qingfeng Yu;Bingsheng Li;F. Strittmatter;A. Herlemann;A. Tamalunas;B. Rutz;A. Ciotkowska;R. Waidelich;Chunxiao Liu;C. Stief;M. Hennenberg

Lenalidomide and pomalidomide inhibit growth of prostate stromal cells and human prostate smooth muscle contraction.

来那度胺和泊马度胺抑制前列腺基质细胞的生长和人前列腺平滑肌收缩

• DOI: 10.1016/j.lfs.2021.119771
• 发表时间: 2021
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: Tamalunas A;Sauckel C;Ciotkowska A;Rutz B;Wang R;Huang R;Stief CG;Gratzke C;Hennenberg M
• 通讯作者: Hennenberg M

Inhibition of human prostate stromal cell growth and smooth muscle contraction by thalidomide: A novel remedy in LUTS?

• DOI: 10.1002/pros.24114
• 发表时间: 2021-03
• 期刊: The Prostate
• 作者: A. Tamalunas;C. Sauckel;A. Ciotkowska;B. Rutz;Ruixiao Wang;Ru Huang;Bingsheng Li;C. Stief

ADP Ribosylation Factor 6 Promotes Contraction and Proliferation, Suppresses Apoptosis and Is Specifically Inhibited by NAV2729 in Prostate Stromal Cells

• DOI: 10.1124/molpharm.121.000304
• 发表时间: 2021-08
• 期刊: Molecular Pharmacology
• 影响因子: 3.6
• 作者: Ruixiao Wang;S. Schneider;O. Keppler;Bingsheng Li;B. Rutz;A. Ciotkowska;C. Stief;M. Hennenberg