Autocrine TGF-β Induces Epithelial to Mesenchymal Transition in Human Amniotic Epithelial Cells

Cell Transplantation

Article

Eva M. García-Vizcaíno¹  Antonia Alcaraz¹  Francisco J. Nicolás¹  Anna Mrowiec¹  Catalina Ruiz-Canada¹  María C. López-Martínez¹  Carmen L. Insausti²  José M. Moraleda² 

[1] Oncología Molecular y TGF-β, Unidad de Investigación, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain;Unidad de Terapia Celular, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain;

关键词: Amniotic membrane (AM);    Epithelial to mesenchymal transition (EMT);    Human amniotic epithelial cells (hAECs);    Transforming growth factor-β (TGF-β);   

DOI  :  10.3727/096368912X657387

 received in 2011-11-23, accepted in 2012-07-07,  发布年份 2013

来源: Sage Journals

【 摘 要 】

Human amniotic epithelial cells (hAECs) have been the object of intense research due to their potential therapeutic use. In this paper, we present molecular evidence of a bona fide epithelial to mesenchymal transition (EMT) undergone by hAECs. Amniotic membrane (AM)-derived hAECs showed the presence of typical epithelial markers such as E-cadherin and cytokeratins. hAECs in culture, however, underwent morphological changes acquiring a mesenchymal shape. Epithelial cell markers were lost and typical mesenchymal markers, such as vimentin and α-SMA, appeared. Several genes associated with EMT, such as SNAI1, MMP9, PAI1, or ACTA2, increased their expression. The expression of the transcription activators KLF4 or MTA3 was consistent with the downregulation of CDH1. We have shown that hAECs undergo EMT due to the autocrine production of TGF-β. Furthermore, the addition of the TGF-β receptor I (ALK5) inhibitor SB-431542 or TGF-β neutralizing antibody to hAECs prevented EMT and preserved the hAECs' epithelial phenotype. Altogether, these results suggest that cultured hAECs undergo EMT through the autocrine production of TGF-β.

【 授权许可】

Unknown   
© 2013 Cognizant Comm. Corp.

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