Diabetes causes multiple genetic alterations and downregulates expression of DNA repair genes in the prostate
Diabetes causes multiple genetic alterations and downregulates expression of DNA repair genes in the prostate
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糖尿病导致多种基因改变并下调前列腺 DNA 修复基因的表达
DOI：
10.1038/labinvest.2011.87
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发表时间：
2011-09-01
影响因子：
5
通讯作者：
Wen, Xingqiao
中科院分区：
文献类型：
--
作者：
Ye, Chunwei;Li, Xiaojuan;Wen, Xingqiao
糖尿病对前列腺的分子影响尚未阐明。在本研究中，我们使用链脲佐菌素诱导的糖尿病大鼠模型进行了全基因组cDNA微阵列分析，以确定糖尿病对前列腺基因表达谱的影响。我们的研究表明，糖尿病引起多个基因表达的变化，特别是那些与细胞增殖和分化，氧化应激，DNA损伤修复，细胞周期检查点，血管生成和凋亡相关的基因。这些发现证实了实时聚合酶链反应和免疫组化染色，使用大鼠和人类前列腺组织。我们还使用细胞培养模型（人正常前列腺RWPE-1细胞系）来研究高糖的直接作用。我们发现，高糖导致细胞内氧化应激和DNA损伤增加，以及抗氧化酶和DNA损伤修复基因MRE 11和XRCC 3下调。我们的研究结果为了解糖尿病引起的前列腺变化的发病机制以及为未来的研究确定潜在的治疗靶点提供了重要的见解。
The molecular impact of diabetes mellitus on prostate gland has not been elucidated. In this study, we performed a whole-genome cDNA microarray analysis using a streptozotocin-induced diabetic rat model to identify the effects of diabetes on the gene expression profiles in prostate. Our study shows that diabetes causes changes in the expression of multiple genes, particularly those related to cell proliferation and differentiation, oxidative stress, DNA damage repair, cell cycle checkpoints, angiogenesis and apoptosis. These findings were confirmed by real-time polymerase chain reaction and immunohistochemical staining using rat and human prostate tissue. We also used a cell culture model (human normal prostatic RWPE-1 cell line) to study the direct effect of high glucose. We found that high glucose caused increased intracellular oxidative stress and DNA damage, as well as downregulation of anti-oxidative enzymes and DNA damage repair genes MRE11 and XRCC3. Our findings provide important insights into understanding the pathogenesis of the diabetes-induced changes in prostate as well as identifying potential therapeutic targets for future studies.