Endothelial cells from different anatomical origin have distinct responses during SNAIL/TGF-β2-mediated endothelial-mesenchymal transition

Mariana Tomazini Pinto, Fernanda Ursoli Ferreira Melo, Tathiane Maistro Malta, Evandra Strazza Rodrigues, Jessica Rodrigues Plaça, Wilson Araújo Silva, Rodrigo Alexandre Panepucci, Dimas Tadeu Covas, Claudia de Oliveira Rodrigues, Simone Kashima

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Endothelial-mesenchymal transition (EndMT) is a complex process whereby differentiated endothelial cells undergo phenotypic transition to mesenchymal cells. EndMT can be stimulated by several factors and the most common are the transforming growth factor-beta (TGF-β) and SNAIL transcription factor. Given the diversity of the vascular system, it is unclear whether endothelial cells lining different vessels are able to undergo EndMT through the same mechanisms. Here we evaluate the molecular and functional changes that occur in different types of endothelial cells following induction of EndMT by overexpression of SNAIL and TGF-β2. Results: We found that responses to induction by SNAIL are determined by cell origin and marker expression. Human coronary endothelial cells (HCAECs) showed the greatest EndMT responses evidenced by significant reciprocal changes in the expression of mesenchymal and endothelial markers, effects that were potentiated by a combination of SNAIL and TGF-β2. Key molecular events associated with EndMT driven by SNAIL/TGF-β2 involved extracellular-matrix remodeling and inflammation (IL-8, IL-12, IGF-1, and TREM-1 signaling). Notch signaling pathway members DLL4, NOTCH3 and NOTCH4 as well as members of the Wnt signaling pathway FZD2, FZD9, and WNT5B were altered in the combination treatment strategy, implicating Notch and Wnt signaling pathways in the induction process. Conclusion: Our results provide a foundation for understanding the roles of specific signaling pathways in mediating EndMT in endothelial cells from different anatomical origins.

Original languageEnglish (US)
Pages (from-to)4065-4081
Number of pages17
JournalAmerican Journal of Translational Research
Volume10
Issue number12
StatePublished - 2018

Keywords

  • Endothelial cells
  • Endothelial-mesenchymal transition (EndMT)
  • SNAIL
  • Transforming growth factor beta 2 (TGF-β2)

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

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    Pinto, M. T., Melo, F. U. F., Malta, T. M., Rodrigues, E. S., Plaça, J. R., Silva, W. A., Panepucci, R. A., Covas, D. T., Rodrigues, C. D. O., & Kashima, S. (2018). Endothelial cells from different anatomical origin have distinct responses during SNAIL/TGF-β2-mediated endothelial-mesenchymal transition. American Journal of Translational Research, 10(12), 4065-4081.