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高脂饮食诱导的前列腺疾病中涉及的炎症信号传导

Inflammatory Signaling Involved in High-Fat Diet Induced Prostate Diseases.

作者信息

Shankar Eswar, Bhaskaran Natarajan, MacLennan Gregory T, Liu Guiming, Daneshgari Firouz, Gupta Sanjay

机构信息

Department of Urology, Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, Ohio 44106 USA.

Department of Pathology, Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, Ohio 44106 USA.

出版信息

J Urol Res. 2015 Jan 1;2(1). Epub 2015 Jan 12.

Abstract

High-Fat Diet (HFD) has emerged as an important risk factor not only for obesity and diabetes but also for urological disorders. Recent research provides ample evidence that HFD is a putative cause for prostatic diseases including prostate cancer. The mechanisms whereby these diseases develop in the prostate have not been fully elucidated. In this review we discuss signaling pathways intricately involved in HFD-induced prostate disease. We performed a search through PUBMED using key words "high fat diet" and "prostate". Our data and perspectives are included in this review along with research performed by various other groups. HFD is positively associated with an increased risk of benign prostatic hyperplasia (BPH) and prostate cancer. HFD induces oxidative stress and inflammation in the prostate gland, and these adverse influences transform it from a normal to a diseased state. Studies demonstrate that HFD accelerates the generation of reactive oxygen species by driving the NADPH oxidase system, exacerbating oxidative stress in the prostate. HFD also causes a significant increase in the levels of pro-inflammatory cytokines and gene products through activation of two important signaling pathways: the Signal Transducer and Activator of Transcription (STAT)-3 and Nuclear Factor-kappa B (NF-κB). Both these pathways function as transcription factors required for regulating genes involved in proliferation, survival, angiogenesis, invasion and inflammation. The crosstalk between these two pathways enhances their regulatory function. Through its influences on the NF-κB and Stat-3 signaling pathways, it appears likely that HFD increases the risk of development of BPH and prostate cancer.

摘要

高脂饮食(HFD)不仅已成为肥胖症、糖尿病的重要风险因素,也是泌尿系统疾病的重要风险因素。最近的研究提供了充分的证据表明,高脂饮食是包括前列腺癌在内的前列腺疾病的一个假定病因。这些疾病在前列腺中发展的机制尚未完全阐明。在这篇综述中,我们讨论了与高脂饮食诱导的前列腺疾病复杂相关的信号通路。我们通过使用关键词“高脂饮食”和“前列腺”在PubMed上进行了检索。我们的数据和观点以及其他各个研究小组的研究成果都包含在本综述中。高脂饮食与良性前列腺增生(BPH)和前列腺癌风险增加呈正相关。高脂饮食会在前列腺中诱导氧化应激和炎症,而这些不利影响会将前列腺从正常状态转变为患病状态。研究表明,高脂饮食通过驱动NADPH氧化酶系统加速活性氧的产生,加剧前列腺中的氧化应激。高脂饮食还通过激活两个重要的信号通路,即信号转导和转录激活因子(STAT)-3和核因子-κB(NF-κB),导致促炎细胞因子和基因产物水平显著增加。这两条信号通路均作为转录因子发挥作用,调控参与细胞增殖、存活、血管生成、侵袭和炎症的基因。这两条信号通路之间的相互作用增强了它们的调控功能。通过对NF-κB和Stat-3信号通路的影响,高脂饮食似乎增加了良性前列腺增生和前列腺癌的发病风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8c/4583131/6e9f4926b773/nihms660627f1.jpg

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