STAT3 mediates bone marrow mesenchymal stem cell VEGF production

Meijing Wang, Wenjun Zhang, Paul Crisostomo, Troy Markel, Kirstan K. Meldrum, Xin Y. Fu, Daniel R. Meldrum

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

The mechanisms by which mesenchymal stem cells (MSCs) may protect native tissue are incompletely understood. Understanding the mechanisms by which these cells release factors such as vascular endothelial growth factor (VEGF), may lead to enhanced protection. We hypothesized that stress, in the form of hypoxia or TNF, activates MSCs to release VEGF by STAT3 and p38 MAPK dependent mechanisms. Mouse MSCs from wild type (WT) and STAT3 knockout mice (STAT3KO) were harvested and purified by a single-step method using adhesion. The release of VEGF was analyzed by using MSC conditioned media under hypoxia or TNF stimulation with or without p38 MAPK inhibition. Activation of STAT3 and p38 MAPK was determined by analysis of cell lysates. MSCs released VEGF under normoxia, which was associated with constitutive STAT3 activity. STAT3 deficiency resulted in decreased MSC production of VEGF. In response to hypoxia or TNF, MSCs produced more VEGF, which was correlated with hypoxia or TNF activated p38 MAPK and STAT3. The p38 MAPK inhibitor significantly decreased hypoxia-induced or TNF-stimulated VEGF production in WT. Additionally, STAT3 ablation neutralized hypoxia-induced MSC release of VEGF. No effect of p38 MAPK inhibitor alone was observed on MSC release of VEGF in WT. However, inhibition of p38 MAPK blocked release of VEGF in STAT3KO MSCs. MSCs are a potent source of VEGF, the production of which is mediated by STAT3 under normoxia partly; however, following hypoxia or TNF exposure, MSC release of VEGF is mediated by both STAT3 and p38 MAPK.

Original languageEnglish (US)
Pages (from-to)1009-1015
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume42
Issue number6
DOIs
StatePublished - Jun 1 2007

Keywords

  • Growth substances
  • Hypoxia
  • Mesenchymal stromal cell
  • Signal transduction
  • STAT3

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Wang, M., Zhang, W., Crisostomo, P., Markel, T., Meldrum, K. K., Fu, X. Y., & Meldrum, D. R. (2007). STAT3 mediates bone marrow mesenchymal stem cell VEGF production. Journal of Molecular and Cellular Cardiology, 42(6), 1009-1015. https://doi.org/10.1016/j.yjmcc.2007.04.010