2. Academic Validation
  3. The KSR1/MEK/ERK signaling pathway promotes the progression of intrauterine adhesions

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

  • Cell Signal. 2025 Mar 13:131:111730. doi: 10.1016/j.cellsig.2025.111730.
Shasha Wu 1,  Qiuhong Chen 1,  Xiao Yang 1,  Lulu Zhang 2,  Xiyue Huang 1,  Jinglin Huang 1,  Jiangling Wu 2,  Congcong Sun 3,  Wenwen Zhang 4,  Jia Wang 5
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China.
  • 2 Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China.
  • 3 Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China. Electronic address: 800344@hospital.cqmu.edu.cn.
  • 4 Department of Pathology, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China. Electronic address: 187254894@qq.om.
  • 5 Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China. Electronic address: 800026@hospital.cqmu.edu.cn.
PMID: 40089092 DOI: 10.1016/j.cellsig.2025.111730
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.

Keywords

Fibrosis; Intrauterine adhesion; Kinase suppressor of Ras 1 (KSR1); MEK/ERK.

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