Vérlemezke-mikro-RNS-ek expressziójának változása thrombocytaaktivációval járó betegségekben

Abstract

MicroRNAs (miRNA) are short, non-coding RNAs consisting of 18–25 nucleotides that regulate posttranscriptionally the gene expression involved in the regulation of physiological processes of the cells. Their key role is to modulate the translation of target mRNAs via binding to complementary sequences within the 3’ UTRs of mRNAs resulting in altered protein synthesis or even the degradation of mRNAs. miRNAs are carried not only by cells with nucleus, but also in platelets, red blood cells, and they are present in the circulation, in urine and in other body fluids as well. The fact about functional miRNAs in platelets without nucleus having a half-life of 8–12 days was questioned for a long time, thus it was also obscure whether platelets are able to produce proteins de novo when being exposed to different challenges. In the last few years, several publications have described the expression and function of certain platelet mRNAs with their regulatory miRNAs in terms of regulation of cell activation, especially in diseases in which platelet activation status is elevated, such as in type 2 diabetes mellitus or in sepsis. Apart from their pathophysiological role, miRNAs may be applied as potential new biomarkers in the investigation or differential diagnosis of these clinical conditions. This review article sought to summarize the recent findings about platelet miRNAs focusing on their altered expression in diabetes and sepsis. Orv Hetil. 2018; 159(47): 1962–1970.

MicroRNA Expression is Associated with Sepsis Disorders in Critically Ill Polytrauma Patients

“…On the other hand, there was an increased expression of microRNA-486 and microRNA-182 in these patients [67]. A similar study carried out by Benz et al, identified important changes in microRNA-233 in patients with sepsis [68]. Other species involved in the molecular and genetic sepsis reactions include microRNA-340, microRNA-324-3p, microRNA-16, microRNA-210, let-7b, microRNA-15b, microRNA-484, microRNA-486-5p, and microRNA-324-3p [69].…”

“…In the next step, RNAse III endonuclease, also called Drosha, activates the pri-microRNAs. This reaction is catalyzed by the DiGeorge Syndrome Critical Region 8 (DGCR8) complex, which leads to the formation of pre-microRNAs [15,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74].…”

“…Once these almost final species are formed, the pre-microRNAs bind with the Exportin-5 transporter protein, which shifts them from the nucleus into the cytoplasm. Inside the cytoplasm, a new reaction, initiated by an RNAse III endonuclease called Dicer and by the RNA binding protein (TRBP), takes place, which leads to the formation of the final microRNA species [17,20,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88]. The last step involves coupling the RNA-induced silencing complex (RISC) [18,78,79,80,81,82,83,84,85,86,87,88,89,90,91].…”

“…Under normal conditions, the human body synthesizes numerous biochemical species with increased reactivity compared to the existent macromolecules. These species are called free radicals and are divided depending on their origin into reactive oxygen species, reactive lipid species, reactive nitrogen species, and other more complex redox systems [20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74]. Biochemically speaking, the most aggressive free radicals are oxygen radicals such as hydroxyl radicals (HO − ), superoxide anions (O 2 − ), or hydrogen peroxide (H 2 O 2 ).…”

“…With regard to the association with infections, oxidative stress has significant implications in increasing the incidence of sepsis due to the release of free radicals, cytokines, and adhesion molecules. Hence, immunosuppression, the increased concentration of pro-inflammatory factors, and the aggressive attack of free radicals all lead to MODS in the critically ill polytrauma patient, despite complex treatment options (Figure 3) [37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85].…”