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富含半胱氨酸的天冬氨酸蛋白水解酶抑制因子Kazal 结构域蛋白 1()基因的表达及其在卵巢子宫内膜异位症中受 miR200b 的调控。

Expression of Reversion-Inducing Cysteine-Rich Protein with Kazal Motifs () Gene and Its Regulation by miR200b in Ovarian Endometriosis.

机构信息

Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, ul. T. Chałubińskiego 5, 02-004 Warsaw, Poland.

1st Department of Obstetrics and Gynecology, Centre for Postgraduate Medical Education, ul. Żelazna 90, 01-004 Warsaw, Poland.

出版信息

Int J Mol Sci. 2024 Oct 29;25(21):11594. doi: 10.3390/ijms252111594.

DOI:10.3390/ijms252111594
PMID:39519143
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11547164/
Abstract

Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient's fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify as a direct target of miR200b. The described effect of miR200b on , together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis.

摘要

子宫内膜异位症是一种常见的慢性疾病,其特征是子宫内膜样组织在子宫腔外生长。该疾病与慢性炎症和盆腔疼痛有关,并且可能对患者的生育能力产生影响。疾病的病因和病理生理学仍未被充分认识。免疫系统失调、组织重塑异常和血管生成有助于疾病的进展。在子宫内膜异位症患者中,调节结缔组织分解和重组的蛋白质,例如胶原酶和其他蛋白酶以及它们的抑制剂,表现出异常的表达模式。在这里,我们报告在与未受影响的女性正常子宫内膜相比,子宫内膜异位症囊肿中,诱导反转的富含半胱氨酸的 Kazal 基序蛋白()的表达升高。我们还证明了 miR200b 在子宫内膜异位组织中的水平降低,与 mRNA 水平相关。此外,我们使用源自腹膜子宫内膜异位病变的 12Z 细胞系和源自子宫内膜腺癌的 Ishikawa 细胞系来鉴定 是 miR200b 的直接靶标。miR200b 对 的这种描述性作用,以及在子宫内膜异位症中这两种基因的异常表达,可能有助于了解组织重塑系统在子宫内膜异位症发病机制中的作用。

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