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Tumor Necrosis Factor α Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB

Anthony R Prisco1,2, Brian R Hoffmann2,3,4, Catherine C Kaczorowski5

  • 1Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.

Stem Cells (Dayton, Ohio)
|February 12, 2016
PubMed

Insights

Tumor necrosis factor alpha (TNFα) enhances endothelial progenitor cell (EPC) migration, a crucial step for blood vessel formation in tissue repair. This study identified NF-kB mediated CADM1 upregulation as the key mechanism.

Area of Science:

  • Cellular and Molecular Medicine
  • Regenerative Medicine
  • Angiogenesis Research

Background:

  • Endothelial progenitor cells (EPCs) hold promise for regenerative medicine, aiming to restore organ function via angiogenesis.
  • Previous clinical trials yielded disappointing results due to an incomplete understanding of EPC-mediated angiogenesis mechanisms.
  • Effective EPC-based therapy requires efficient migration and homing to damaged tissues.

Purpose of the Study:

  • To investigate the role of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) in EPC migration.
  • To test the hypothesis that inflammation signals from organ damage promote EPC homing.
  • To elucidate the molecular mechanisms underlying TNFα-induced EPC migration.

Main Methods:

  • In vitro coculture assay to model EPC migration towards vessel-like structures.
  • Treatment of EPCs with TNFα to assess migration and incorporation.
  • Genomic and proteomic analyses to identify molecular mediators of TNFα-induced migration.

Main Results:

  • TNFα treatment significantly increased EPC migration and incorporation into vessel-like structures.
  • NF-kB mediated upregulation of CADM1 was identified as a key mechanism for TNFα-induced EPC migration.
  • Inhibition of NF-kB or CADM1 markedly reduced EPC migration in vitro.

Conclusions:

  • TNFα signaling plays a critical role in promoting EPC homing to sites of tissue damage.
  • The NF-kB/CADM1 pathway is essential for TNFα-induced EPC migration.
  • Understanding these mechanisms could improve the efficacy of EPC-based therapies for ischemic diseases.
Keywords:
CADM1Cellular migrationEndothelial progenitor cellsTNFα

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