Upregulation of androgen-responsive genes and transforming growth factor-β1 cascade genes in a rat model of non-bacterial prostatic inflammation.
Upregulation of androgen-responsive genes and transforming growth factor-β1 cascade genes in a rat model of non-bacterial prostatic inflammation.
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DOI：
10.1002/pros.22668
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发表时间：
2014-04
期刊：
影响因子：
2.8
通讯作者：
Yoshimura, Naoki
中科院分区：
文献类型：
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作者：
Funahashi, Yasuhito;O'Malley, Katherine J.;Kawamorita, Naoki;Tyagi, Pradeep;DeFranco, Donald B.;Takahashi, Ryosuke;Gotoh, Momokazu;Wang, Zhou;Yoshimura, Naoki
前列腺炎症与前列腺增生的发生有关。我们研究了前列腺炎症对前列腺中雄激素反应基因和生长因子表达水平的影响。雄性SD大鼠前列腺腹侧叶注射福尔马林诱导前列腺炎症。28天后，收集前列腺用于分析促炎细胞因子、上皮中的雄激素应答基因和基质中的TGF-β1级联基因。一些大鼠经口灌胃给予考克斯-2抑制剂（塞来昔布; 10 mg/kg/天），持续28天。注射福尔马林的前列腺显示出广泛的低度炎症（< 50个白细胞/10，000 μm2），沿着局部高度炎症（> 100个白细胞/10，000 μm2）。与对照组相比，福尔马林注射的前列腺显示IL-1α、IL-1β和IL-6的蛋白表达增加2.5-6倍。在低度炎症区，通过激光捕获显微切割获得的上皮和间质中分别观察到雄激素受体/雄激素应答基因和TGF-β1级联基因的mRNA水平上调3-9倍和2-3倍。轻度炎症区上皮细胞核雄激素受体、间质中TGF-β1、IL-6和考克斯-2阳性染色增加。考克斯-2抑制剂处理抑制了这些细胞因子、雄激素应答和TGF-β1级联基因的上调。前列腺炎症诱导上皮中雄激素反应基因和间质中TGF-β1级联基因表达增加，这些基因被考克斯-2抑制剂抑制，表明这些基因在低度炎症区域的激活可能参与了症状性BPH的发展。
Prostatic inflammation is associated with the development of prostatic hyperplasia. We investigated the effects of prostatic inflammation on expression levels of androgen-responsive genes and growth factors in the prostate. Prostatic inflammation was induced by formalin injection into bilateral ventral lobes of the prostate of male SD rats. After 28 days, the prostate was harvested for analyses of proinflammatory cytokines, androgen-responsive genes in the epithelium and TGF-β1 cascade genes in the stroma. Some rats were given a COX-2 inhibitor (celecoxib; 10 mg/kg/day) by oral gavage for 28 days. The formalin-injected prostate exhibited widespread low-grade inflammation (< 50 leukocytes/10,000 μm2) along with focal high-grade inflammation (> 100 leukocytes/10,000 μm2) in limited areas. Compared to control, formalin-injected prostate exhibited a 2.5–6 fold increased protein expression of IL-1α, IL-1β, and IL-6. In the low-grade inflammatory regions, 3–9 fold and 2–3 fold upregulations of mRNA levels of androgen receptors/androgen-responsive genes and TGF-β1 cascade genes were respectively observed in the epithelium and stroma obtained by laser-capture microdissection. Positive staining for androgen receptors in the epithelial nuclei, and TGF-β1, IL-6 and COX-2 in the stroma was increased in the low-grade inflammation area. COX-2 inhibitor treatment suppressed these upregulations of cytokines, androgen-responsive and TGF-β1 cascade genes. Prostatic inflammation induced increased expression of androgen-responsive genes in the epithelium and TGF-β1 cascade genes in the stroma, which were suppressed by COX-2 inhibitors, suggesting that activation of these genes in the low-grade inflammatory region might be involved in the development of symptomatic BPH.
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DOI：
10.1002/pros.21081
发表时间：
2010-04-01
期刊：
The Prostate
影响因子：
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作者：
Fujita K;Ewing CM;Getzenberg RH;Parsons JK;Isaacs WB;Pavlovich CP
通讯作者：
Pavlovich CP
影响因子：
2.8
作者：
Robert, Gregoire;Descazeaud, Aurelien;de la Taille, Alexandre
通讯作者：
de la Taille, Alexandre
影响因子：
2.8
作者：
Haverkamp, Jessica M.;Charbonneau, Bridget;Crist, Scott A.;Meyerholz, David K.;Cohen, Michael B.;Snyder, Paul W.;Svensson, Robert U.;Henry, Michael D.;Wang, Hsing-Hui;Ratliff, Timothy L.
通讯作者：
Ratliff, Timothy L.
影响因子：
23.4
作者：
Nickel, J. Curtis;Roehrborn, Claus G.;Rittmaster, Roger S.
通讯作者：
Rittmaster, Roger S.
影响因子：
2.9
作者：
McLaren, Ian D.;Jerde, Travis J.;Bushman, Wade
通讯作者：
Bushman, Wade