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

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Tác giả: Qiuhong Chen, Jinglin Huang, Xiyue Huang, Congcong Sun, Jia Wang, Jiangling Wu, Shasha Wu, Xiao Yang, Lulu Zhang, Wenwen Zhang

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Cellular signalling , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 714034

Ras kinase suppressor 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-ERK, 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.
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