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

American Journal of Translational Research

Ev¹  a Ursoli Ferreira Melo²  Fern³  ra Strazza Rodrigues⁴  Tathiane Maistro Malta⁵  Mariana Tomazini Pinto⁶ 

[1]Department of Molecular and Cellular Pharmacology, University of Miami Leonard M, Miller School of Medicine, Miami, Florida, USA

[2]Faculty of Medicine of Ribeiro Preto, University of So Paulo, Ribeiro Preto, Brazil

[3]Faculty of Pharmaceutical Sciences, University of So Paulo, Ribeiro Preto, Brazil

[4]Interdisciplinary Stem Cell Institute, University of Miami Leonard M, Miller School of Medicine, Miami, Florida, USA

[5]Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil

[6]National Institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-Based Therapy and Regional Blood Center of Ribeiro Preto, Brazil

关键词: Endothelial-mesenchymal transition (EndMT);    endothelial cells;    SNAIL;    transforming growth factor beta 2 (TGF-β;    2);   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

CC BY-NC