The role of macrophage migration inhibitory factor in promoting benign prostatic hyperplasia epithelial cell growth by modulating COX-2 and P53 signaling.
The role of macrophage migration inhibitory factor in promoting benign prostatic hyperplasia epithelial cell growth by modulating COX-2 and P53 signaling.
复制标题
巨噬细胞迁移抑制因子通过调节COX-2和P53信号促进良性前列腺增生上皮细胞生长的作用
DOI：
10.1242/bio.053447
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发表时间：
2020-11-12
期刊：
影响因子：
2.4
通讯作者：
Jin J
中科院分区：
文献类型：
--
作者：
Song H;Shen Q;Hu S;Jin J
摘要炎症和促炎细胞因子与良性前列腺增生（BPH）的进展有关。巨噬细胞迁移抑制因子（MIF）是一种促炎细胞因子。我们前期的研究发现MIF在BPH上皮细胞中高表达。据报道，MIF 与临床 BPH 进展之间存在相关性。然而，MIF是否对BPH上皮细胞有影响尚不清楚。本研究的目的是探讨 MIF 是否在 BPH 中发挥作用。我们的结果表明，免疫组织化学 (IHC) 显示 MIF 在上皮细胞中高表达，并且 BPH 样本中的 MIF 和 PCNA 表达水平高于对照。 CCK8和流式细胞术检测表明，重组人MIF (rMIF)促进BPH-1和PWR-1E细胞的增殖，而ISO-1部分逆转了这种对增殖的影响。 JC-1实验表明rMIF抑制BPH-1和PWR-1E细胞的凋亡，而ISO-1可以部分逆转这种抑制作用。此外，蛋白质印迹表明rMIF下调P53并上调COX-2。此外，在 CCK8 和流式细胞术测定中，塞来昔布可以抑制 MIF 诱导的增殖。在 JC-1 测定中，塞来昔布可以部分逆转 MIF 抑制的细胞凋亡。 Western blotting显示塞来昔布可以部分逆转MIF诱导的COX-2上调和P53下调。总之，MIF 在 BPH 上皮细胞中高度表达。在体外，MIF 通过调节 COX-2 和 P53 信号传导促进 BPH 上皮细胞生长。靶向MIF可能为未来改善BPH治疗提供新的选择。摘要：本研究发现 BPH 上皮细胞中 MIF 表达水平较高。 MIF通过调节COX-2和P53信号促进BPH上皮细胞生长并参与BPH的进展
ABSTRACT Inflammation and proinflammatory cytokines have been implicated in the progression of benign prostatic hyperplasia (BPH). Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine. Our previous study found that MIF is highly expressed in BPH epithelium. It has been reported that there is a correlation between MIF and clinical BPH progression. However, whether MIF has an effect on BPH epithelial cells is not clear. The aim of this study was to explore whether MIF has a role in BPH. Our results showed that immunohistochemistry (IHC) showed that MIF is highly expressed in the epithelium and that MIF and PCNA expression levels are higher in BPH samples than in control. CCK8 and flow cytometry assays showed that recombinant human MIF (rMIF) promoted the proliferation of BPH-1 and PWR-1E cells, while ISO-1 partially reversed this effect on proliferation. JC-1 assays showed that rMIF inhibited the apoptosis of BPH-1 and PWR-1E cells, and ISO-1 could partially reverse this inhibition. Moreover, western blotting indicated that rMIF downregulated P53 and upregulated COX-2. Furthermore, MIF-induced proliferation could be inhibited by celecoxib in the CCK8 and flow cytometry assay. MIF-inhibited apoptosis could be partially reversed by celecoxib in the JC-1 assay. Western blotting showed that celecoxib could partially reverse MIF-induced COX-2 upregulation and P53 downregulation. Together, MIF is highly expressed in BPH epithelium. In vitro, MIF promoted BPH epithelial cell growth by regulating COX-2 and P53 signaling. Targeting MIF may provide a new option for the improved treatment of BPH in the future. Summary: This study found high levels of MIF expression in BPH epithelium. MIF promoted BPH epithelial cell growth and participated in the progression of BPH by regulating COX-2 and P53 signaling