Endothelial Mesenchymal Transition: Comparative Analysis of Different Induction Methods

Autor(es)

Pinto, Mariana T. ^{[1, 2, 3, 4]} ; Covas, Dimas T. ^{[5, 2, 3]} ; Kashima, Simone ^{[1, 2, 3]} ; Rodrigues, Claudia O. ^{[4, 6]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Inst Nacl Ciencia & Tecnol Celulas Tronco & Terap, Ribeirao Preto, SP - Brazil

^[3] Fundacao Hemoctr Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[4] Univ Miami, Leonard M Miller Sch Med, Interdisciplinary Stem Cell Inst, Biomed Res Bldg, 1501 NW 10th Ave, Room 826, Miami, FL 33136 - USA

^[5] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP - Brazil

^[6] Univ Miami, Leonard M Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 - USA

• Tipo de documento: Artigo Científico
• Fonte: BIOLOGICAL PROCEDURES ONLINE; v. 18, APR 27 2016.
• Citações Web of Science: 13

Resumo

Background: Endothelial-Mesenchymal-Transition (EndMT) plays an essential role in cardiovascular development, and recently became an attractive therapeutic target based on evidence supporting its involvement in fibrosis and cancer. Important questions that remain to be answered are related to the molecular mechanisms that control EndMT in different organs and distinct pathological conditions. The lack of a detailed protocol for induction of EndMT and the assumption that TGF-beta isoforms play similar roles on different types of endothelial cells, limit progress in the field. The aim of this study was to compare the induction of EndMT by TGF-beta isoforms in endothelial cells of different sources, and define a detailed protocol for EndMT assessment in vitro. Results: We compared the dose-dependent effect of TGF-beta isoforms, under normoxia and hypoxia, on the induction of EndMT in human coronary and pulmonary artery endothelial cells. Our results suggest that endothelial cells undergo spontaneous EndMT with time in culture under the conditions tested. The extent of EndMT induction by TGF-beta was dependent on the dose and endothelial cell type. Furthermore, the potential of TGF-beta to induce EndMT was reduced under hypoxia relative to normoxia. Conclusions: Our work suggests that the response of endothelial cells to TGF-beta is intrinsic to the dose, cell type and environment. Optimization of induction conditions may be essential, as pathways triggering EndMT may vary during development and pathological conditions. Therefore, caution is needed regarding indiscriminate use of TGF-beta to induce EndMT for mechanistic studies. (AU)

• 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