The KSR1/MEK/ERK signaling pathway promotes the progression of intrauterine adhesions

IF 4.4 2区 生物学 Q2 CELL BIOLOGY
Shasha Wu , Qiuhong Chen , Xiao Yang , Lulu Zhang , Xiyue Huang , Jinglin Huang , Jiangling Wu , Congcong Sun , Wenwen Zhang , Jia Wang
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引用次数: 0

Abstract

Kinase suppressor of Ras 1 (KSR1) serves as a scaffold protein within the RAS-RAF pathway and plays a role in tumorigenesis, immune regulation, cell proliferation, and apoptosis. However, the specific role of KSR1 in the formation and progression of fibrotic diseases, such as intrauterine adhesions (IUA), remains unclear. This study aims to investigate KSR1 expression in IUA and the mechanisms underlying its role in promoting IUA progression. KSR1 was found to be significantly overexpressed in the endometrium of both IUA model rats and patients with IUA. KSR1 is positively involved in the regulation of proliferation, migration, and fibrosis (FN1, Collagen I, α-SMA) in immortalized human endometrial stromal cells (THESCs). Furthermore, KSR1 knockdown was observed to inhibit the fibrosis, proliferation, and migration of transforming growth factor-β1 (TGF-β1)-induced THESCs. Further studies demonstrated that the key proteins of the MEK/ERK signaling pathway, p-MEK1 and p-ERK1/2, were significantly overexpressed in the uterus of IUA rats. In vitro rescue experiments confirmed that the MEK/ERK pathway inhibitor U0126 (An ERK inhibitor) effectively suppressed the enhanced fibrosis, proliferation, and migration induced by KSR1 overexpression. In conclusion, this study demonstrates that KSR1 promotes IUA by enhancing proliferation, migration, and fibrosis of endometrial stromal cells via the MEK/ERK signaling pathway.
KSR1/MEK/ERK信号通路促进宫内粘连的进展。
Ras激酶抑制因子1 (Ras kinase suppressor 1, KSR1)是Ras - raf通路中的一种支架蛋白,在肿瘤发生、免疫调节、细胞增殖和凋亡等过程中发挥作用。然而,KSR1在纤维化疾病(如宫内粘连(IUA))的形成和进展中的具体作用尚不清楚。本研究旨在探讨KSR1在IUA中的表达及其促进IUA进展的机制。KSR1在IUA模型大鼠和IUA患者的子宫内膜中均显著过表达。KSR1积极参与永生化人子宫内膜基质细胞(THESCs)增殖、迁移和纤维化(FN1,胶原I, α-SMA)的调节。此外,KSR1敲低可抑制转化生长因子-β1 (TGF-β1)诱导的THESCs的纤维化、增殖和迁移。进一步研究表明,MEK/ERK信号通路的关键蛋白p-MEK1和p-ERK在IUA大鼠子宫中显著过表达。体外拯救实验证实MEK/ERK通路抑制剂U0126 (An ERK inhibitor)能有效抑制KSR1过表达诱导的纤维化、增殖和迁移增强。综上所述,本研究表明KSR1通过MEK/ERK信号通路促进子宫内膜间质细胞的增殖、迁移和纤维化,从而促进IUA。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cellular signalling
Cellular signalling 生物-细胞生物学
CiteScore
8.40
自引率
0.00%
发文量
250
审稿时长
27 days
期刊介绍: Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.
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