TY  - JOUR
AU  - Gatica, Sebastian
AU  - Eltit, Felipe
AU  - Santibanez, Juan F.
AU  - Varela, Diego
AU  - Cabello-Verrugio, Claudio
AU  - Simon, Felipe
PY  - 2019
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/905
AB  - Background: Main pathological features detected during sepsis and endotoxemia include over-secretion of pro-inflammatory cytokines and multiorgan dysfunction syndrome (MODS). Unfortunately, current clinical efforts to treat sepsis are unsatisfactory, and mortality remains high. Interestingly, transient receptor potential (TRP) melastatin 7 (TRPM7) ion channel controlling Ca2+ and Mg2+ permeability is involved in cytokine production and inflammatory response. Furthermore, TRPM7 downregulation has been shown to alleviate local symptoms in some models of sepsis, but its effects at a systemic level remain to be explored. Objective: To test whether TRPM7 mediates cytokine production and MODS during endotoxemia. Methods: Endotoxemic and sham-endotoxemic rats were subjected to pharmacological inhibition of TRPM7 using carvacrol, or to expression suppression by adenovirus delivery of shRNA (AdV(shTRPM7)). Then, cytokine and MODS levels in the blood were measured. Results: Inhibition of TRPM7 with carvacrol and suppression with AdV(shTRPM7 )were both efficient in inhibiting the over-secretion of pro-inflammatory cytokines TNF-alpha, IL-1 beta, IL-6, and IL-12 in endotoxemic rats, without inducing downregulation in blood levels of anti-inflammatory cytokines IL-10 and IL-4. Additionally, the use of carvacrol and AdV(shTRPM7) significantly prevented liver and pancreas dysfunction, altered metabolic function, and hypoglycemia, induced by endotoxemia. Furthermore, muscle mass wasting and cardiac muscle damage were also significantly reduced by the use of carvacrol and AdV(shTRPM7) in endotoxemic rats. Conclusion: Our results indicate TRPM7 ion channel as a key protein regulating inflammatory responses and MODS during sepsis. Moreover, TRPM7 appears as a novel molecular target for the management of sepsis.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Molecular Medicine
T1  - Expression Suppression and Activity Inhibition of TRPM7 Regulate Cytokine Production and Multiple Organ Dysfunction Syndrome During Endotoxemia: A New Target for Sepsis
EP  - 559
IS  - 8
SP  - 547
VL  - 19
DO  - 10.2174/1566524019666190709181726
ER  - 

@article{
author = "Gatica, Sebastian and Eltit, Felipe and Santibanez, Juan F. and Varela, Diego and Cabello-Verrugio, Claudio and Simon, Felipe",
year = "2019",
abstract = "Background: Main pathological features detected during sepsis and endotoxemia include over-secretion of pro-inflammatory cytokines and multiorgan dysfunction syndrome (MODS). Unfortunately, current clinical efforts to treat sepsis are unsatisfactory, and mortality remains high. Interestingly, transient receptor potential (TRP) melastatin 7 (TRPM7) ion channel controlling Ca2+ and Mg2+ permeability is involved in cytokine production and inflammatory response. Furthermore, TRPM7 downregulation has been shown to alleviate local symptoms in some models of sepsis, but its effects at a systemic level remain to be explored. Objective: To test whether TRPM7 mediates cytokine production and MODS during endotoxemia. Methods: Endotoxemic and sham-endotoxemic rats were subjected to pharmacological inhibition of TRPM7 using carvacrol, or to expression suppression by adenovirus delivery of shRNA (AdV(shTRPM7)). Then, cytokine and MODS levels in the blood were measured. Results: Inhibition of TRPM7 with carvacrol and suppression with AdV(shTRPM7 )were both efficient in inhibiting the over-secretion of pro-inflammatory cytokines TNF-alpha, IL-1 beta, IL-6, and IL-12 in endotoxemic rats, without inducing downregulation in blood levels of anti-inflammatory cytokines IL-10 and IL-4. Additionally, the use of carvacrol and AdV(shTRPM7) significantly prevented liver and pancreas dysfunction, altered metabolic function, and hypoglycemia, induced by endotoxemia. Furthermore, muscle mass wasting and cardiac muscle damage were also significantly reduced by the use of carvacrol and AdV(shTRPM7) in endotoxemic rats. Conclusion: Our results indicate TRPM7 ion channel as a key protein regulating inflammatory responses and MODS during sepsis. Moreover, TRPM7 appears as a novel molecular target for the management of sepsis.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Molecular Medicine",
title = "Expression Suppression and Activity Inhibition of TRPM7 Regulate Cytokine Production and Multiple Organ Dysfunction Syndrome During Endotoxemia: A New Target for Sepsis",
pages = "559-547",
number = "8",
volume = "19",
doi = "10.2174/1566524019666190709181726"
}

Gatica, S., Eltit, F., Santibanez, J. F., Varela, D., Cabello-Verrugio, C.,& Simon, F.. (2019). Expression Suppression and Activity Inhibition of TRPM7 Regulate Cytokine Production and Multiple Organ Dysfunction Syndrome During Endotoxemia: A New Target for Sepsis. in Current Molecular Medicine
Bentham Science Publ Ltd, Sharjah., 19(8), 547-559.
https://doi.org/10.2174/1566524019666190709181726

Gatica S, Eltit F, Santibanez JF, Varela D, Cabello-Verrugio C, Simon F. Expression Suppression and Activity Inhibition of TRPM7 Regulate Cytokine Production and Multiple Organ Dysfunction Syndrome During Endotoxemia: A New Target for Sepsis. in Current Molecular Medicine. 2019;19(8):547-559.
doi:10.2174/1566524019666190709181726 .

Gatica, Sebastian, Eltit, Felipe, Santibanez, Juan F., Varela, Diego, Cabello-Verrugio, Claudio, Simon, Felipe, "Expression Suppression and Activity Inhibition of TRPM7 Regulate Cytokine Production and Multiple Organ Dysfunction Syndrome During Endotoxemia: A New Target for Sepsis" in Current Molecular Medicine, 19, no. 8 (2019):547-559,
https://doi.org/10.2174/1566524019666190709181726 . .