Endotoxin induces fibrosis in vascular endothelial cells through a mechanism dependent on transient receptor protein melastatin 7 activity
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2014-04
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Facultad/escuela
Idioma
en
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Public Library of Science
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Atribution 4.0 International (CC BY 4.0)
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https://creativecommons.org/licenses/by/4.0/deed.es
Resumen
The pathogenesis of systemic inflammatory diseases, including endotoxemia-derived sepsis syndrome, is characterized by
endothelial dysfunction. It has been demonstrated that the endotoxin lipopolysaccharide (LPS) induces the conversion of
endothelial cells (ECs) into activated fibroblasts through endothelial-to-mesenchymal transition mechanism. Fibrogenesis is
highly dependent on intracellular Ca2+ concentration increases through the participation of calcium channels. However, the
specific molecular identity of the calcium channel that mediates the Ca2+ influx during endotoxin-induced endothelial
fibrosis is still unknown. Transient receptor potential melastatin 7 (TRPM7) is a calcium channel that is expressed in many
cell types, including ECs. TRPM7 is involved in a number of crucial processes such as the conversion of fibroblasts into
activated fibroblasts, or myofibroblasts, being responsible for the development of several characteristics of them. However,
the role of the TRPM7 ion channel in endotoxin-induced endothelial fibrosis is unknown. Thus, our aim was to study
whether the TRPM7 calcium channel participates in endotoxin-induced endothelial fibrosis. Using primary cultures of ECs,
we demonstrated that TRPM7 is a crucial protein involved in endotoxin-induced endothelial fibrosis. Suppression of TRPM7
expression protected ECs from the fibrogenic process stimulated by endotoxin. Downregulation of TRPM7 prevented the
endotoxin-induced endothelial markers decrease and fibrotic genes increase in ECs. In addition, TRPM7 downregulation
abolished the endotoxin-induced increase in ECM proteins in ECs. Furthermore, we showed that intracellular Ca2+ levels
were greatly increased upon LPS challenge in a mechanism dependent on TRPM7 expression. These results demonstrate
that TRPM7 is a key protein involved in the mechanism underlying endotoxin-induced endothelial fibrosis.
Notas
Indexación: Scopus.
Palabras clave
Transfection, Fibrosis, Endotoxins, Endothelial cells, Fibroblasts, Calcium Channels, Small Interfering RNA, Membrane Proteins
Citación
PLoS ONE. Volume 9, Issue 4. 7 April 2014 Article number e94146
DOI
DOI: 10.1371/journal.pone.0094146