Ailevi Akdeniz Ateşi Hastalığında Görülen İnflamasyon Sürecinde Rol Alan Mirna'ların Tanımlanması

Abstract

Familial Mediterranean Fever (FMF); is an autosomal recessively inherited autoinflammatory disease. FMF is caused by the mutations in the Mediterranean Fever (MEFV) gene which encodes the pyrin protein. The best treatment for the disease is daily colchicine treatment. In many studies, pyrin has been implicated in important cellular processes; Apoptosis, cytoskeleton dynamics, signal transduction, and inflammation. Recent studies have shown that epigenetic control mechanisms, particularly non-coding RNAs, may play a role in the pathogenesis of autoinflammation. MicroRNAs (miRNAs) which is a group of non-coding RNAs have been shown to have activating or repressing properties in the inflammatory response process. Therefore, we hypothesized that miRNAs those have roles in inflammatory pathways may be important for the pathogenesis of the FMF disease. In this thesis study; miRNA isolation was done from blood samples taken from selected control and patient groups. miRNA expression analysis was performed by miRNA 2.0 array analysis. Candidate miRNAs were classified according to their roles in cytokine secretion or apoptosis or cell migration pathways. In this context, miR-20a and miR-197 were identified as two candidate miRNAs. Functional studies for identifying the functions of two candidate miRNAs were performed in two different cell lines that naturally express the MEFV gene. As a result of functional analysis, miR-197 was found to be involved in many inflammatory pathways. Subsequently, target gene studies for this miRNA were performed. miR-197 was found to bind to the interleukin-1beta (IL-1β) receptor, type I (IL1R1), which is one of the key molecules of the inflammatory pathways. Thus, this study may contribute to understand the inflammatory process seen in FMF disease, as well as to development of the new drug targets and biomarkers in addition to the existing colchicine and similar treatments.