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雌激素调节良性前列腺增生中初级基质细胞的增殖和炎症表达。

Estrogen regulates the proliferation and inflammatory expression of primary stromal cell in benign prostatic hyperplasia.

作者信息

Chen Bo, Cao Dehong, Chen Zeyu, Huang Yin, Lin Tianhai, Ai Jianzhong, Liu Liangren, Wei Qiang

机构信息

Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.

Institution of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Transl Androl Urol. 2020 Apr;9(2):322-331. doi: 10.21037/tau.2020.02.08.

Abstract

BACKGROUND

To investigate the expression of estrogen receptor (ER) in prostate tissues of benign prostatic hyperplasia (BPH) individuals, and the effects of estrogen regulating the proliferation and inflammatory expressions of primary prostate stromal cells in BPH.

METHODS

A total of 44 human BPH prostate tissues were collected to explore the expression of ER by immunohistochemistry (IHC). Cell proliferation, mRNA and protein expressions were analyzed in primary prostate stromal cells treated with estrogen or estrogen plus fulvestrant through cell count kit-8 (CCK-8) assay, quantitative real-time polymerase chain reaction (qPCR), IHC and western blot, respectively.

RESULTS

Firstly, ERβ was positive, and ERα was negative in the transition zone of prostate among all the 44 individuals with BPH. Secondly, the effects could be partially inhibited by fulvestrant, of estrogen promoting the proliferation of primary prostate stromal cells cultured in dulbecco's modified eagle medium (DMEM) supplemented with 2% fetal bovine serum (FBS). Thirdly, estrogen up-regulates the mRNA levels of C-C chemokine receptor type 3 (CCR3), CD40 ligand (CD 40L), C-X-C motif chemokine ligand 9 (CXCL9) and interleukin 10 (IL10), and down-regulates the mRNA levels of C-C chemokine receptor type 4 (CCR4) and interleukin 17C (IL17C). Then, the protein expressions of CCR3, CCR4, CD40L, IL10 and IL17C are positive, and CXCL9 is negative in the third-generation primary prostate stromal cells. Finally, the effects could be partially inhibited by fulvestrant, of estrogen up-regulating the protein levels of CD40L and IL10.

CONCLUSIONS

The expressions of ER in human BPH prostate tissues are zone-dependent. Estrogen promoting the proliferation of primary prostate stromal cells cultured in DMEM supplemented with 2% FBS. The expressions of CCR3, CCR4, CD 40L, IL17C, CXCL9 and IL10 are regulated by estrogen in primary prostate stromal cells.

摘要

背景

研究雌激素受体(ER)在良性前列腺增生(BPH)患者前列腺组织中的表达,以及雌激素对BPH患者原代前列腺基质细胞增殖和炎症表达的影响。

方法

收集44例人BPH前列腺组织,采用免疫组织化学(IHC)法检测ER的表达。分别通过细胞计数试剂盒-8(CCK-8)法、定量实时聚合酶链反应(qPCR)、IHC和蛋白质印迹法分析雌激素或雌激素加氟维司群处理的原代前列腺基质细胞的细胞增殖、mRNA和蛋白质表达。

结果

首先,在所有44例BPH患者中,前列腺移行带中ERβ呈阳性,ERα呈阴性。其次,氟维司群可部分抑制雌激素促进在添加2%胎牛血清(FBS)的杜氏改良 Eagle培养基(DMEM)中培养的原代前列腺基质细胞增殖的作用。第三,雌激素上调C-C趋化因子受体3(CCR3)、CD40配体(CD40L)、C-X-C基序趋化因子配体9(CXCL9)和白细胞介素10(IL10)的mRNA水平,下调C-C趋化因子受体4(CCR4)和白细胞介素17C(IL17C)的mRNA水平。然后,在第三代原代前列腺基质细胞中,CCR3、CCR4、CD40L、IL10和IL17C的蛋白质表达呈阳性,CXCL9呈阴性。最后,氟维司群可部分抑制雌激素上调CD40L和IL10蛋白质水平的作用。

结论

人BPH前列腺组织中ER的表达具有区域依赖性。雌激素促进在添加2%FBS的DMEM中培养的原代前列腺基质细胞增殖。原代前列腺基质细胞中CCR3、CCR4、CD40L、IL17C、CXCL9和IL10的表达受雌激素调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a8f/7214965/e0281194aed4/tau-09-02-322-f1.jpg

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