Differential expression and regulation of vitamin D hydroxylases and inflammatory genes in prostate stroma and epithelium by 1,25-dihydroxyvitamin D in men with prostate cancer and an in vitro model.
Differential expression and regulation of vitamin D hydroxylases and inflammatory genes in prostate stroma and epithelium by 1,25-dihydroxyvitamin D in men with prostate cancer and an in vitro model.
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DOI：
10.1016/j.jsbmb.2014.10.004
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发表时间：
2015-04
影响因子：
4.1
通讯作者：
Nonn, Larisa
中科院分区：
文献类型：
--
作者：
Giangreco, Angeline A.;Dambal, Shweta;Wagner, Dennis;Van der Kwast, Theodorus;Vieth, Reinhold;Prins, Gail S.;Nonn, Larisa
以前关于前列腺中维生素D的工作集中在前列腺上皮，前列腺癌就是从前列腺上皮产生的。前列腺上皮细胞被基质包围，基质对上皮细胞增殖、分化和炎症反应具有良好的调节控制。在这里，我们研究了1α，25-二羟维生素D3（1，25（OH）2D）在激光捕获显微切割的前列腺组织中对维生素D相关基因和炎症基因的调节，这些前列腺组织来自维生素D3临床试验和促进基质-上皮串扰的体外模型。试验组织的分析表明，VDR存在于两种细胞类型中，而羟化酶的表达在上皮中最高。通过前列腺（1，25（OH）2D）浓度检测基因表达显示，在1，25（OH）2D浓度最高的前列腺组织中，VDR显著降低，并且在原代细胞培养物中证实了1，25（OH）2D对VDR的下调。对患者组织中炎性基因的分析显示，IL-6表达在前列腺基质中最高，而PTGS 2（COX 2）水平在前列腺1，25（OH）2D最高三分位数的男性前列腺癌组织中最低。1，25（OH）2D对原代上皮细胞中TNF-α、IL-6和IL-8的表达有抑制作用，对基质细胞中TNF-α和PTGS 2的表达有抑制作用。重要的是，1，25（OH）2D改变促炎诱导的上皮细胞生长变化的能力取决于基质细胞的存在。总之，尽管前列腺的基质细胞和上皮细胞都表达VDR，并且可以推测对1，25（OH）2D产生应答，但1，25（OH）2D似乎主要由前列腺上皮产生。此外，虽然前列腺上皮比基质细胞对1，25（OH）2D的抗炎活性更敏感，但基质-上皮串扰增强了1，25（OH）2D的表型效应和前列腺中的炎症过程。
Previous work on vitamin D in the prostate has focused on the prostatic epithelium, from which prostate cancer arises. Prostatic epithelial cells are surrounded by stroma, which has well-established regulatory control over epithelial proliferation, differentiation, and the inflammatory response. Here we examined the regulation of vitamin D-related genes and inflammatory genes by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D) in laser-capture microdissected prostate tissue from a vitamin D3 clinical trial and in an in vitro model that facilitates stromal–epithelial crosstalk. Analysis of the trial tissues showed that VDR was present in both cell types, whereas expression of the hydroxylases was the highest in the epithelium. Examination of gene expression by prostatic (1,25(OH)2D) concentrations showed that VDR was significantly lower in prostate tissues with the highest concentration of 1,25(OH)2D, and down-regulation of VDR by 1,25(OH) 2D was confirmed in the primary cell cultures. Analysis of inflammatory genes in the patient tissues revealed that IL-6 expression was the highest in the prostate stroma while PTGS2 (COX2) levels were lowest in the prostate cancer tissues from men in the highest tertile of prostatic 1,25(OH)2D. In vitro, TNF-α, IL-6 and IL-8 were suppressed by 1,25 (OH)2D in the primary epithelial cells, whereas TNF-α and PTGS2 were suppressed by 1,25(OH) 2D in the stromal cells. Importantly, the ability of 1,25(OH)2D to alter pro-inflammatory-induced changes in epithelial cell growth were dependent on the presence of the stromal cells. In summary, whereas both stromal and epithelial cells of the prostate express VDR and can presumably respond to 1,25(OH)2D, which appears to be primarily produced by the prostatic epithelium. Further, while the prostate epithelium was more responsive to the anti-inflammatory activity of 1,25 (OH)2D than stromal cells, stroma–epithelial crosstalk enhanced the phenotypic effects of 1,25(OH)2D and the inflammatory process in the prostate gland.
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DOI：
10.1016/j.jsbmb.2006.12.072
发表时间：
2007-03-01
影响因子：
4.1
作者：
Hidalgo, Alejandro A.;Paredes, Roberto;Onate, Sergio A.
通讯作者：
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DOI：
10.1016/j.jsbmb.2011.05.009
发表时间：
2011-11-01
影响因子：
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作者：
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DOI：
10.1016/j.urolonc.2007.05.007
发表时间：
2007-09-01
影响因子：
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影响因子：
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作者：
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