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Human Endometrium Derived Mesenchymal Stem Cells with Aberrant NOD1 Expression Are Associated with Ectopic Endometrial Lesion Formation

  • Chunmei Li (Department of Gynecology and Obstetrics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital) ;
  • Suiyu Luo (Department of Gynecology and Obstetrics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital) ;
  • Ai Guo (Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College) ;
  • Ying Su (Department of Gynecology and Obstetrics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital) ;
  • Yuhui Zhang (Department of Gynecology and Obstetrics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital) ;
  • Yan Song (Department of Gynecology and Obstetrics, Women & Infants Hospital of Zhengzhou) ;
  • Mei Liu (Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College) ;
  • Lu Wang (Department of Gynecology and Obstetrics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital) ;
  • Yuanyuan Zhang (Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
  • Received : 2022.12.09
  • Accepted : 2024.01.08
  • Published : 2024.08.30

Abstract

Nucleotide-binding oligomerization domain 1 (NOD1), a cytosolic pattern recognition receptor protein, plays a crucial role in innate immune responses. However, the functional expression of NOD1 in mesenchymal stem cells (MSCs) derived from endometriosis remains unclear. The aim of this study was to explore the functions of NOD1 in ectopic endometrial lesions. Tissues and MSCs were isolated from both normal endometrium and endometriosis. Immunohistochemistry and real time quantitative polymerase chain reaction (RT-qPCR) were used to determine the expression of NOD1 in the tissues/MSCs. Quantification of various cytokines was performed using RT-qPCR and enzyme-linked immunosorbent assay. To confirm the proliferation, invasion/migration, and apoptotic viabilities of the samples, Cell Counting Kit-8, clonogenic formation, transwell assays, and apoptotic experiments were conducted. Higher levels of NOD1 expression were detected in the ectopic-MSCs obtained from endometriosis compared to those from the endometrium. The expression of interleukin-8 was higher in the ectopic-MSCs than in the eutopic-MSCs. Pretreatment with NOD1 agonist significantly enhanced the proliferation and invasion/migration of eutopic-MSCs. Additionally, the NOD1 inhibitor ML-130 significantly reduced the proliferation, clone formation, invasion, and migration abilities of the ectopic-MSCs, having no effect on their apoptosis capacity. Our findings suggest that the expression of NOD1 in ectopic-MSCs may contribute to the progression of ectopic endometrial lesions.

Keywords

Acknowledgement

This work was supported by the National Natural Science Foundation of China (81601261, 82173333), Henan Province Medical Science and Technology Project (LHGJ20190596), and Science and Technology Development Plan (202102310066).

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