Endotoxin-induced endothelial fibrosis is dependent on expression of transforming growth factors β1 and β2

César Echeverría, Ignacio Montorfano, Pablo Tapia, Claudia Riedel, Claudio Cabello-Verrugio, Felipe Simon

Resultado de la investigación: Contribución a una revistaArtículo

22 Citas (Scopus)

Resumen

During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate in the bloodstream and interact with endothelial cells (ECs), inducing dysfunction of the ECs. We previously reported that endotoxins induce the conversion of ECs into activated fibroblasts. Through endotoxin-induced endothelial fibrosis, ECs change their morphology and their protein expression pattern, thereby suppressing endothelial markers and upregulating fibrotic proteins. The most commonly used fibrotic inducers are transforming growth factor β1 (TGF-β1) and TGF-β2. However, whether TGF-β1 and TGF-β2 participate in endotoxin- induced endothelial fibrosis remains unknown. We have shown that the endotoxin-induced endothelial fibrosis process is dependent on the TGF-β receptor, ALK5, and the activation of Smad3, a protein that is activated by ALK5 activation, thus suggesting that endotoxin elicits TGF-β production to mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the dependence of endotoxin-induced endothelial fibrosis on the expression of TGF-β1 and TGF-β2. Endotoxin-treated ECs induced the expression and secretion of TGF-β1 and TGF-β2. TGF-β1 and TGF-β2 downregulation inhibited the endotoxininduced changes in the endothelial marker VE-cadherin and in the fibrotic proteins α-SMA and fibronectin. Thus, endotoxin induces the production of TGF-β1 and TGF-β2 as a mechanism to promote endotoxin-induced endothelial fibrosis. To the best of our knowledge, this is the first report showing that endotoxin induces endothelial fibrosis via TGF-β secretion, which represents an emerging source of vascular dysfunction. These findings contribute to understanding the molecular mechanism of endotoxin- induced endothelial fibrosis, which could be useful in the treatment of inflammatory diseases.

Idioma originalInglés
Páginas (desde-hasta)3678-3686
Número de páginas9
PublicaciónInfection and Immunity
Volumen82
N.º9
DOI
EstadoPublicada - 2014

Áreas temáticas de ASJC Scopus

  • Inmunología
  • Microbiología
  • Parasitología
  • Enfermedades infecciosas

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