17 beta-estradiol inhibits cardiac fibroblast growth through both subtypes of estrogen receptor.
17 beta-estradiol inhibits cardiac fibroblast growth through both subtypes of estrogen receptor.
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DOI：
10.1016/j.bbrc.2003.09.232
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发表时间：
2003-11
影响因子：
3.1
通讯作者：
Tokumitsu Watanabe;M. Akishita;Hong He;Y. Miyahara;K. Nagano;T. Nakaoka;N. Yamashita;K. Kozaki;Y. Ouchi
中科院分区：
文献类型：
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作者：
Tokumitsu Watanabe;M. Akishita;Hong He;Y. Miyahara;K. Nagano;T. Nakaoka;N. Yamashita;K. Kozaki;Y. Ouchi
17β-雌二醇（E2）对心脏成纤维细胞（CFs）增殖的影响仍存在争议。本研究利用腺病毒载体进行功能分析，探讨雌激素受体（ER）的哪一种亚型（ERα或ERβ）介导E2对CF生长的影响。100纳摩尔/升的E2衰减DNA合成高达10%，并反式激活雌激素反应元件在大鼠新生儿CFs荧光素酶测定。我们构建了携带人ERα、ERβ或ERβ显性阴性形式编码区的复制缺陷型腺病毒（分别命名为AxCAERα、AxCAERβ和AxCADNERβ）。当用AxCAERα或AxCAERβ以20或更高的感染复数感染CF时，响应于E2，DNA合成减少50%，并且与AxCADNERβ共感染消除了该效果。同样，AxCAERα或AxCAERβ感染的CFs中ER的转录活性显著增强，与AxCADNERβ共感染则消除了这种作用。这些结果表明，E2抑制CF的生长和两个ER亚型介导的效果重复和冗余。
The effect of 17β-estradiol (E2) on the proliferation of cardiac fibroblasts (CFs) remains controversial. This study investigated which subtype of estrogen receptor (ER), ERα or ERβ, mediated the effect of E2 on CF growth by the gain of function analysis using an adenovirus vector. One hundred nanomoles per liter of E2 attenuated DNA synthesis by up to 10%, and transactivated the estrogen-responsive element determined by luciferase assay in rat neonatal CFs. We constructed replication-deficient adenoviruses bearing the coding region of human ERα, ERβ, or the dominant-negative form of ERβ (designated AxCAERα, AxCAERβ, and AxCADNERβ, respectively). When CFs were infected with AxCAERα or AxCAERβ at multiplicity of infection of 20 or higher, DNA synthesis was decreased by 50% in response to E2 and the effect was abolished by co-infection with AxCADNERβ. Similarly, transcriptional activity of ER in CFs infected with AxCAERα or AxCAERβ was markedly enhanced and co-infection with AxCADNERβ abolished the effects. These results suggest that E2 inhibits CF growth and that both ER subtypes mediate the effect comparably and redundantly.