Effect of estradiol on fibroblasts from postmenopausal idiopathic carpal tunnel syndrome patients

Effect of estradiol on fibroblasts from postmenopausal idiopathic carpal tunnel syndrome patients
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DOI:
10.1002/jcp.26752
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发表时间:
2018-11-01
影响因子:
5.6
通讯作者:
Sakai,Akinori
Sakai,Akinori
中科院分区:
生物学2区
文献类型:
--
作者:
Yamanaka,Yoshiaki;Menuki,Kunitaka;Sakai,Akinori

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滑膜下结缔组织(SSCT)纤维化是特发性腕管综合征(CTS)患者的特征性表现。特发性CTS经常发生在绝经后妇女,因此,女性类固醇激素,特别是雌激素,可能参与其发展。在这项研究中,我们评估了雌二醇对特发性CTS患者SSCT成纤维细胞纤维化相关基因和蛋白表达的影响。该研究包括10名绝经后女性(平均年龄76岁)。用雌二醇(10−4-10− 12 M)处理来自SSCT的成纤维细胞,并评估TGF-β反应基因的表达水平。通过定量真实的时间聚合酶链反应检测未经处理的雌激素受体α(ERα)和ERβ的表达与雌二醇处理引起的基因表达变化之间的关系。还通过荧光染色评价了10− 4 M雌二醇对I型胶原(Col 1)和III型胶原(Col 3)蛋白表达水平的影响。采用免疫组化方法检测ERα/β与Col 1/3表达的关系。雌激素处理后Col 1A 1 mRNA表达降低与ERα表达呈正相关(r= 0.903,p < 0.01)。在蛋白质水平上,Col 1和Col 3的表达下调。这些结果表明ERα介导的信号通路可能参与了Col 1A 1的调控,其调控作用可能依赖于ERα的表达水平。准确评价特发性CTS患者SSCT中ERα的表达水平可能有助于指导新的雌激素替代疗法的有效应用。
Fibrosis of the subsynovial connective tissue (SSCT) is a characteristic finding in patients with idiopathic carpal tunnel syndrome (CTS). Idiopathic CTS frequently occurs in postmenopausal women; therefore, female steroid hormones, especially estrogens, may be involved in its development. In this study, we evaluated the effect of the estradiol on the expression of genes and proteins related to fibrosis of SSCT fibroblasts from patients with idiopathic CTS. This study included 10 postmenopausal women (mean age 76 years). Fibroblasts derived from SSCT were treated with estradiol (10−4–10−12M), and the expression levels of TGF‐β‐responsive genes were evaluated. The relationships between the expression of untreated estrogen receptor α (ERα) and ERβ and changes in gene expression due to estradiol treatment were examined by quantitative real‐time polymerase chain reaction. The effects of 10−4M estradiol on collagen type I (Col1) and collagen type III (Col3) protein expression levels were also evaluated by fluorescent staining. The relationships between ERα/β and Col1/3 expression were evaluated by immunohistochemical staining. The reduction in Col1A1 mRNA expression due to estradiol treatment was positively correlated with ERα expression (r= 0.903,p< 0.01). At the protein level, expression of Col1 and Col3 were down‐regulated. These results indicated that ERα‐mediated signaling may be involved in the regulation of Col1A1, and its regulatory effect may be dependent on the ERα expression level. The accurate evaluation of ERα expression level in the SSCT of individual patients with idiopathic CTS might guide the effective use of new estrogen replacement therapy.