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白细胞介素 6 对微小 RNA-21 的调控及其在子宫内膜异位症病灶纤维化发展中的作用。

The Regulation of MicroRNA-21 by Interleukin-6 and Its Role in the Development of Fibrosis in Endometriotic Lesions.

机构信息

Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USA.

Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA.

出版信息

Int J Mol Sci. 2024 Aug 19;25(16):8994. doi: 10.3390/ijms25168994.

Abstract

Endometriosis is one of the most common causes of chronic pelvic pain and infertility that affects 10% of women of reproductive age. It is currently defined as the presence of endometrial epithelial and stromal cells at ectopic sites; however, advances in endometriosis research have some authors believing that endometriosis should be re-defined as "a fibrotic condition in which endometrial stroma and epithelium can be identified". microRNAs (miRNAs) are regulatory molecules that potentially play a role in endometriotic lesion development. There is evidence that suggests that miRNAs, including microRNA-21 (miR-21), participate in fibrotic processes in different organs, including the heart, kidney, liver and lungs. The objective of this study was to understand the role of miR-21 and the mechanisms that can contribute to the development of fibrosis by determining how IL-6 regulates miR-21 expression and how this miRNA regulates the transforming growth factor beta () signaling pathway to promote fibrosis. We investigated the expression of miR-21 in the baboon and mouse model of endometriosis and its correlation with fibrosis. We demonstrated that inflammation and fibrosis are present at a very early stage of endometriosis and that the inflammatory environment in the peritoneal cavity, which includes interleukin 6 (IL-6), can regulate the expression of miR-21 in vitro and in vivo.

摘要

子宫内膜异位症是导致慢性盆腔痛和不孕的最常见原因之一,影响着 10%的育龄妇女。目前,它被定义为子宫内膜上皮和基质细胞在异位部位的存在;然而,子宫内膜异位症研究的进展使一些作者认为,子宫内膜异位症应该重新定义为“一种纤维性疾病,其中可以识别子宫内膜基质和上皮”。microRNAs(miRNAs)是潜在参与子宫内膜异位症病变发展的调节分子。有证据表明,miRNAs,包括 microRNA-21(miR-21),参与不同器官(包括心脏、肾脏、肝脏和肺部)的纤维化过程。本研究的目的是通过确定 IL-6 如何调节 miR-21 的表达以及该 miRNA 如何调节转化生长因子β(TGF-β)信号通路来促进纤维化,来了解 miR-21 的作用及其促进纤维化发展的机制。我们研究了 miR-21 在狒狒和小鼠子宫内膜异位症模型中的表达及其与纤维化的相关性。我们证明了炎症和纤维化在子宫内膜异位症的早期阶段就存在,并且包括白细胞介素 6(IL-6)在内的腹腔内炎症环境可以在体外和体内调节 miR-21 的表达。

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