BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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p38 mitogen-activated protein kinase contributes to TNFα-induced endothelial tube formation of bone-marrow-derived mesenchymal stem cells by activating the JAK/STAT/TIE2 signaling axis

  • Sukjin Ou (Department of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University) ;
  • Tae Yoon Kim (Department of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University) ;
  • Euitaek Jung (Department of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University) ;
  • Soon Young Shin (Department of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University)
  • Received : 2023.08.22
  • Accepted : 2023.10.28
  • Published : 2024.05.31
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Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into endothelial cells in an inflammatory microenvironment. However, the regulatory mechanisms underlying this process are not entirely understood. Here, we found that TIE2 in BM-MSCs was upregulated at the transcriptional level after stimulation with tumor necrosis factor-alpha (TNFα), a major pro-inflammatory cytokine. Additionally, the STAT-binding sequence within the proximal region of TIE2 was necessary for TNFα-induced TIE2 promoter activation. TIE2 and STAT3 knockdown reduced TNFα-induced endothelial tube formation in BM-MSCs. Among the major TNFα-activated MAP kinases (ERK1/2, JNK1/2, and p38 MAPK) in BM-MSCs, only inhibition of the p38 kinase abrogated TNFα-induced TIE2 upregulation by inhibiting the JAK-STAT signaling pathway. These findings suggest that p38 MAP contributes to the endothelial differentiation of BM-MSCs by activating the JAK-STAT-TIE2 signaling axis in the inflammatory microenvironment.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT) (grant no. 2023R1A2C1003601). This study was supported by the KU Research Professor Program at Konkuk University.

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