Echeverría, CésarMontorfano, IgnacioTapia, PabloRiedel, ClaudiaCabello-Verrugio, ClaudioSimon, Felipe2023-07-212023-07-212014Infection and Immunity. Volume 82, Issue 9, Pages 3678 - 3686. 20140019-9567https://repositorio.unab.cl/xmlui/handle/ria/51908Indexación: Scopus.During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate in the bloodstream and interact with endo thelial 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 expres sion pattern, thereby suppressing endothelial markers and upregulating fibrotic proteins. The most commonly used fibrotic in ducers are transforming growth factor 1 (TGF- 1) and TGF- 2. However, whether TGF- 1 and TGF- 2 participate in endo toxin-induced endothelial fibrosis remains unknown. We have shown that the endotoxin-induced endothelial fibrosis process is dependent on the TGF- receptor, ALK5, and the activation of Smad3, a protein that is activated by ALK5 activation, thus sug gesting that endotoxin elicits TGF- production to mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the dependence of endotoxin-induced endothelial fibrosis on the expression of TGF- 1 and TGF- 2. Endotoxin-treated ECs induced the expression and secretion of TGF- 1 and TGF- 2. TGF- 1 and TGF- 2 downregulation inhibited the endotoxin induced changes in the endothelial marker VE-cadherin and in the fibrotic proteins -SMA and fibronectin. Thus, endotoxin in duces the production of TGF- 1 and TGF- 2 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- secretion, which represents an emerging source of vascular dysfunction. These findings contribute to understanding the molecular mechanism of endotox in-induced endothelial fibrosis, which could be useful in the treatment of inflammatory diseasesenEndothelial FibrosisEndothelial Cells (ECs)TGF- β2TGF-β1)Inflammatory DiseaseBacterial EndotoxinsArtículoAtribution 4.0 International (CC BY 4.0)10.1128/IAI.02158-14