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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells

Abstract: The lysyl oxidase (LOX) family encodes the copper-dependent amine oxidases that play a key role in determining the tensile strength and structural integrity of connective tissues by catalyzing the crosslinking of elastin or collagen. Estrogen may upregulate the expression of LOX and lysyl oxidase-like 1 (LOXL1) in the vagina. The objective of this study was to determine the effect of estrogen on the expression of all LOX family genes in the urogenital tissues of accelerated ovarian aging mice and human Ishikawa cells. Mice and Ishikawa cells treated with estradiol (E2) showed increased expression of LOX family genes and transforming growth factor β1 (TGF-β1). Ishikawa cells treated with TGF-β1 also showed increased expression of LOX family genes. The Ishikawa cells were then treated with either E2 plus the TGF-β receptor (TGFBR) inhibitor SB431542 or E2 alone. The expression of LOX family genes induced by E2 was reduced in the Ishikawa cells treated with TGFBR inhibitor. Our results showed that E2 increased the expression of the LOX family genes, and suggest that this induction may be mediated by the TGF-β signal pathway. E2 may play a role in regulating the expression of LOX family genes.

Key words: Estradiol, Lysyl oxidase family genes, TGF-β signal pathway

Chinese Summary  <18> 雌激素对赖氨酰氧化酶(LOX)家族基因表达的影响

目的:探讨雌激素对小鼠泌尿生殖系统以及人子宫内膜癌细胞系中的LOX家族基因表达的影响。
创新点:系统地研究了雌二醇在小鼠泌尿生殖系统(子宫、阴道和膀胱)以及人子宫内膜癌细胞系中对LOX家族基因表达的影响;提出了转化生长因子-β(TGF-β)信号通路可能在雌二醇调节LOX家族中发挥作用。
方法:使用雌二醇对卵巢快速衰老小鼠和人子宫内膜癌细胞系进行处理,然后通过荧光实时定量聚合酶链式反应(PCR),分别从体内和体外研究雌二醇对LOX家族基因表达的影响(图2~5)。在人子宫内膜癌细胞系中加入TGF-β1,通过荧光实时定量PCR,检测LOX家族基因表达的变化(图6)。利用人子宫内膜癌细胞系为对象,进行分组研究:一组无任何处理,为对照组;一组只加雌二醇;一组则同时加入雌二醇和TGF-β受体抑制剂(SB431542)。24小时后,检测LOX家族基因及TGF-β1的表达(图6)。
结论:雌二醇可以促进卵巢快速衰老小鼠和人子宫内膜癌细胞系中LOXLOXL1LOXL2LOXL3LOXL4TGF-β1表达的升高,其中雌二醇很有可能是通过TGF-β信号通路影响LOX家族基因的表达量。由于LOX家族基因与盆腔疾病关系密切,所以我们的发现可能为临床上盆腔器官疾病的预防和治疗提供一些理论基础。

关键词组:赖氨酰氧化酶(LOX)家族基因;雌二醇;TGF-β信号通路


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DOI:

10.1631/jzus.B1500048

CLC number:

Q95

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On-line Access:

2015-10-03

Received:

2015-02-26

Revision Accepted:

2015-05-07

Crosschecked:

2015-09-13

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