Molecular mechanisms of organ damage in sepsis: an overview
AUTOR(ES)
Sygitowicz, Grażyna; Sitkiewicz, Dariusz
FONTE
Braz J Infect Dis
DATA DE PUBLICAÇÃO
2020-12
RESUMO
ABSTRACT Sepsis is one of the most common reasons for hospitalization. This condition is characterized by systemic inflammatory response to infection. International definition of sepsis mainly points out a multi-organ dysfunction caused by a deregulated host response to infection. An uncontrolled inflammatory response, often referred to as "cytokine storm", leads to an increase in oxidative stress as a result of the inhibition of cellular antioxidant systems. Oxidative stress, as well as pro-inflammatory cytokines, initiate vascular endothelial dysfunction and, in consequence, impair microcirculation. Microcirculation damage leads to adaptive modifications of cell metabolism. Moreover, mitochondrial dysfunction takes place which results in increased apoptosis and organ damage. Non-coding RNA fragments, especially miRNA molecules, may play an important role in the pathomechanism of sepsis. Numerous studies have indicated altered expression of various miRNAs in sepsis. miRNAs can be used as markers in the diagnosis and prognosis of disease development. In turn, intracellular miRNAs regulate the TLR4/NFκB pathway responsible for the expression of pro-inflammatory cytokine genes involved in the inflammatory response in sepsis. The understanding of detailed molecular mechanisms leading to organ damage can contribute to the development of specific therapy methods thereby improving the prognosis of patients with sepsis.
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