Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition

International Journal of Molecular Sciences

Fernanda Ursoli Ferreira¹  Mariana Tomazini Pinto¹  Lucas Eduardo Botelho Souza¹  Carolina Hassibe Thomé¹  Suellen Salustiano¹  Simone Kashima¹  Dimas Tadeu Covas¹  Vitor Marcel Faça²  Clarice Origassa³  Niels Olsen Câmara³ 

[1] Center for Cell Based Therapy, Regional Blood Center, Ribeirão Preto 14051-140, Brazil;Department of Biochemistry and Immunology, FMRP-University of São Paulo, Ribeirão Preto, SP 14049-900, Brazil;Institute of Biomedical Sciences, University São Paulo, São Paulo 05508-900, Brazil;

关键词: endothelial cells;    TGF-β2;    endothelial-mesenchymal transition;    epithelial-mesenchymal transition;    signaling pathways;   

DOI  :  10.3390/ijms20030458

来源: DOAJ

【 摘 要 】

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 β (TGF-β) 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-β2 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-β2. We observed that among the ECs analyzed in this study, PAECs showed the best response to the TGF-β2 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⁻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.

【 授权许可】

Unknown