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热休克转录因子 1 通过上调磷酸果糖激酶-4 样蛋白 3 的表达促进子宫内膜异位症的发展和糖酵解。

HSF1 promotes endometriosis development and glycolysis by up-regulating PFKFB3 expression.

机构信息

Department of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, People's Republic of China.

出版信息

Reprod Biol Endocrinol. 2021 Jun 9;19(1):86. doi: 10.1186/s12958-021-00770-9.

Abstract

BACKGROUND

Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which brings physical and mental pain to patients and their families.

METHODS

We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count assay, cell-scratch assay and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect HSF1 expression. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we used a HSF1 inhibitor-KRIBB11 to establish a mouse model of endometriosis.

RESULTS

Our data demonstrated that HSF1 promoted endometriosis development. Interestingly, HSF1 enhanced glycolysis via up-regulating PFKFB3 expression in endometriosis cells, which was a key glycolysis enzyme. Consistently, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro.

CONCLUSIONS

Findings indicate that HSF1 plays an important role in endometriosis development, which might become a new target for the treatment of endometriosis.

ELECTRONIC SUPPLEMENTARY MATERIAL

Supplementary data are available.

摘要

背景

子宫内膜异位症是一种慢性激素炎症性疾病,其特征是子宫内膜组织出现在子宫以外的部位。子宫内膜异位症常导致不孕,给患者及其家庭带来身心痛苦。

方法

我们通过细胞计数实验、细胞划痕实验和克隆形成实验来研究热休克因子 1(HSF1)在子宫内膜异位症发展中的作用。我们使用实时定量 PCR(qRT-PCR)和 Western blot(WB)检测 HSF1 的表达。使用葡萄糖测定试剂盒和乳酸测定试剂盒测定葡萄糖和乳酸水平。此外,我们使用 HSF1 抑制剂-KRIBB11 建立了子宫内膜异位症的小鼠模型。

结果

我们的数据表明 HSF1 促进了子宫内膜异位症的发展。有趣的是,HSF1 通过上调子宫内膜异位症细胞中 PFKFB3 的表达来增强糖酵解,PFKFB3 是一种关键的糖酵解酶。同样,HSF1 抑制剂 KRIBB11 可以在体内和体外阻断子宫内膜异位症的进展。

结论

研究结果表明,HSF1 在子宫内膜异位症的发展中起着重要作用,它可能成为治疗子宫内膜异位症的新靶点。

电子补充材料:补充数据可在网上获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88b0/8188696/55b8c2e4f936/12958_2021_770_Fig1_HTML.jpg

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