1. Endothelial cells tissue-specific origins affects their responsiveness to TGF-β2 during endothelial-to-mesenchymal transition
- Author
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Fernanda Ursoli Ferreira, Simone Kashima, Niels Olsen Saraiva Câmara, Mariana T. Pinto, Suellen Salustiano, Dimas Tadeu Covas, Carolina Hassibe Thomé, Clarice Silvia Taemi Origassa, Lucas Eduardo Botelho de Souza, and Vitor M. Faça
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,epithelial-mesenchymal transition ,Cell junction ,Catalysis ,Umbilical vein ,Article ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,Transforming Growth Factor beta2 ,0302 clinical medicine ,FIBROBLASTOS ,TGF-β2 ,Human Umbilical Vein Endothelial Cells ,endothelial-mesenchymal transition ,Humans ,Epithelial–mesenchymal transition ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Cells, Cultured ,Chemistry ,Organic Chemistry ,Mesenchymal stem cell ,General Medicine ,Flow Cytometry ,endothelial cells ,signaling pathways ,Computer Science Applications ,Cell biology ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Tumor progression ,030220 oncology & carcinogenesis ,Signal transduction ,Transforming growth factor ,Signal Transduction - Abstract
The endothelial-to-mesenchymal transition (EndMT) is a biological process where endothelial cells (ECs) acquire a fibroblastic phenotype after concomitant loss of the apical-basal polarity and intercellular junction proteins. This process is critical to embryonic development and is involved in diseases such as fibrosis and tumor progression. The signaling pathway of the transforming growth factor &beta, (TGF-&beta, ) is an important molecular route responsible for EndMT activation. However, it is unclear whether the anatomic location of endothelial cells influences the activation of molecular pathways responsible for EndMT induction. Our study investigated the molecular mechanisms and signaling pathways involved in EndMT induced by TGF-&beta, 2 in macrovascular ECs obtained from different sources. For this purpose, we used four types of endothelial cells (coronary artery endothelial cells, CAECs, primary aortic endothelial cells PAECs, human umbilical vein endothelia cells, HUVECs, and human pulmonary artery endothelial cells, HPAECs) and stimulated with 10 ng/mL of TGF-&beta, 2. We observed that among the ECs analyzed in this study, PAECs showed the best response to the TGF-&beta, 2 treatment, displaying phenotypic changes such as loss of endothelial marker and acquisition of mesenchymal markers, which are consistent with the EndMT activation. Moreover, the PAECs phenotypic transition was probably triggered by the extracellular signal&ndash, regulated kinases 1/2 (ERK1/2) signaling pathway activation. Therefore, the anatomical origin of ECs influences their ability to undergo EndMT and the selective inhibition of the ERK pathway may suppress or reverse the progression of diseases caused or aggravated by the involvement EndMT activation.
- Published
- 2019