In the organs of patients experiencing endotoxemia-derived sepsis syndrome. TRPM7 has been found to be Tubulin Acetylation Inducer HDAC inhibitor involved in a number of human diseases and pathological conditions, including the activation of immune system cells, brain ischemia, Guamanian lateral sclerosis and Parkinson’s, atrial fibrillation, and cancer. The majority of these pathologies are characterized by an Kinase Inhibitor Library increase in the intracellular level of ROS. Similarly, increases in oxidative stress are a common consequence of inflammatory processes, and it has been reported that LPS induces an increase in intracellular ROS levels in ECs. In addition, TRPM7 activity has been found to be regulated by oxidative stress, and the expression of TRPM7 is increased in cells exposed to oxidant agents. Interestingly, endotoxin-induced endothelial fibrosis is prevented by treatment with the reducing agent N-acetylcysteine. Considering these findings, it can be suggested that the participation of TRPM7 in the endotoxin-induced endothelial fibrosis could be mediated by the ROS generated by 
LPS challenge. Further experiments are needed to shed light on this issue. An interesting feature of TRPM7 is that it contains a C-terminal Ser/Thr kinase domain. As we demonstrated that suppression of TRPM7 expression is necessary for endotoxininduced endothelial fibrosis in the present study, it is possible that the kinase activity of the channel could also be involved in the induction of endothelial fibrosis. However, further experiments will certainly be needed to verify this hypothesis. Changes in intracellular Ca2+ concentrations are essential for diverse cellular processes to occur normally. However, several lines of evidence suggest that alterations of Ca2+ levels are also essential for the development of pathological conditions. Considering that an increase in intracellular Ca2+ is fundamental for fibrogenesis to take place, we sought to study this issue. The endotoxin-induced intracellular Ca2+ increase was characterized by a transient elevation of Ca2+ and a rapid return to basal calcium levels, suggesting the existence of a negative feedback mechanism regulating the Ca2+ increase. The experiments involving siRNA-TRPM7 demonstrated that the endotoxininduced Ca2+ increase was mediated through TRPM7. Experiments performed using MCI-186 and L-NAME suggest that hydroxyl radical, super oxide and peroxynitrite, but not nitric oxide, could be involved in the endotoxin-induced Ca2+ increase. Furthermore, since the inhibition of the endotoxin-induced Ca2+ increase produced by NAC and GSH, it is possible to hypothesize that the oxidative modifications produced in TRPM7 could be performed in thiol groups from cysteine residues. These findings suggest either that TRPM7 directly participates in the mechanism regulating the endotoxin-induced Ca2+ increase or that other TRPM7-related proteins are involved in the regulation of the TRPM7-mediated calcium influx. In this context, a non-selective cation channel, TRPM4, has been shown to be involved in the regulation of intracellular calcium overloading and oscillations by controlling the plasma membrane potential. Thus, TRPM4 activity indirectly controls the calcium influx, which is mediated by additional calcium channels regulating intracellular calcium homeostasis to promote physiological and pathological processes. ECM proteins are produced and secreted in balance with their degradation in healthy.