Endothelial cells from different anatomical origin have distinct responses during SNAIL/TGF-beta 2-mediated endothelial-mesenchymal transition

Autor(es)

Pinto, Mariana Tomazini ^{[1, 2, 3]} ; Ferreira Melo, Fernanda Ursoli ^[2] ; Malta, Tathiane Maistro ^[2] ; Rodrigues, Evandra Strazza ^[2] ; Placa, Jessica Rodrigues ^[2] ; Jr Silva, Wilson Araujo ; Panepucci, Rodrigo Alexandre ^{[4, 5]} ; Covas, Dimas Tadeu ^{[4, 5]} ; Rodrigues, Claudia de Oliveira ^{[6, 7]} ; Kashima, Simone ^{[4, 3]}

Afiliação do(s) autor(es)

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[2] Ctr Cell Based Therapy & Reg Blood Ctr Ribeirao P, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Tenente Catao Roxo St 2501, BR-14051140 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Pharmaceut Sci, Ribeirao Preto - Brazil

^[4] Jr Silva, Jr., Wilson Araujo, Ctr Cell Based Therapy & Reg Blood Ctr Ribeirao P, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Tenente Catao Roxo St 2501, BR-14051140 Ribeirao Preto, SP - Brazil

^[5] Jr Silva, Jr., Wilson Araujo, Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto - Brazil

^[6] Univ Miami, Leonard M Miller Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL - USA

^[7] Univ Miami, Leonard M Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL - USA

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH; v. 10, n. 12, p. 4065-4081, 2018.
• Citações Web of Science: 2

Resumo

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-beta) 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-beta 2. 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-132. Key molecular events associated with EndMT driven by SNAIL/TGF-beta 2 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. (AU)

• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/21740-7 - Avaliação dos fatores de transcrição indutores da transição epitélio-mesenquimal (EMT) na biologia das células endoteliais
• Beneficiário: Mariana Tomazini Pinto
• Modalidade de apoio: Bolsas no Brasil - Doutorado