Further investigations are required to determine the exact role of these site-specific methylation changes and other epigenetic modifications like histone methylation and or acetylation on macrophage differentiation. In summary, KLF4 promoter undergoes active DNA demethylation CPI-613 95809-78-2 During monocyte/macrophage differentiation and AICDA plays an essential role in this demethylation process. Sepsis syndrome is the most prevalent cause of mortality in critically ill patients Silmitasertib PKC inhibitor admitted to intensive care units. The pathogenesis of sepsis syndrome develops through an overactivation of the immune system, which involves activation of immune cells, secretion of pro-inflammatory cytokines and generation of reactive oxygen species. Despite numerous basic and clinical studies addressing sepsis syndrome, current therapies for treating it and its sequelae are unsatisfactory, exhibiting high morbimortality rates. Endotoxemia-derived sepsis syndrome is a important cause of sepsis syndrome. It is frequently characterized by deposition of large amounts of the Gram-negative bacterial endotoxin, lipopolysaccharide. During endotoxemia, the endotoxin circulating in the bloodstream interacts with the endothelial cells located in the internal endothelial monolayer of blood vessels, inducing detrimental effects on endothelium function. It is well accepted that the endothelial dysfunction is an important factor in the pathogenesis of endotoxemia-derived sepsis syndrome as well as other inflammatory diseases. We reported that LPS induces at least two main effects in vascular ECs. First, endotoxin promotes 
endothelial cell death. Second, LPS is able to induce the conversion of ECs into activated fibroblasts, also known as myofibroblasts. Endotoxin-induced endothelial fibrosis is mediated through a process known as endothelial-to-mesenchymal transition in a similar way that observed using the best-studied EndMT inducers, tumor growth factor- beta 1 and 2. Determining the molecular entity that mediates the Ca2+ influx during fibrogenesis is an issue of great importance due to its therapeutic implications. It has been reported that L-type calcium channels modulate perivascular fibrosis in the kidney. Similarly, it has been reported that blocking of T-type and Ltype calcium channels is effective in decreasing tubulointerstitial fibrosis. Furthermore, cardiac fibrosis was found to be decreased when calcium channel blockers were used in addition to complementary treatments. The results provided here contribute to our understanding of the molecular basis of endotoxin-induced endothelial fibrosis, revealing a novel target that could be useful in drug development for treating endothelial dysfunction during endotoxemia and other inflammatory diseases. Endothelial dysfunction is a hallmark of the progression of sepsis syndrome and several inflammatory diseases. Because the current available therapies are often not satisfactory, the identification of key proteins involved in these pathologies is essential for improving their treatment. We previously reported that the endotoxin LPS induces endothelial fibrosis. Here, we delved deeper into the molecular mechanism underlying in the endotoxin-induced endothelial fibrosis. In endotoxemia-derived sepsis syndrome, large amounts of LPS are found in the bloodstream, directly interacting with ECs.