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Expression of microRNAs involved in the inflammatory response in monocytes of sickle cell disease patients with and without leg ulcers

Grant number: 12/21116-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2013
Effective date (End): October 19, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Maria de Fatima Sonati
Grantee:Magnun Nueldo Nunes dos Santos
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Leg ulcer is a debilitating complication and is associated with the increased of morbimortality in sickle cell anemia (SCA) patients. However, the advances in understanding the pathophysiology and management of leg ulcers are developing slowly. Several genetic factors have been shown to be important in modulating the clinical presentation of SCA and other candidates are emerging as possible modulators, such as microRNAs (miRNAs) that are small single stranded RNA molecules of 18-22 nucleotides non-protein-coding that regulate the expression of their target genes post-transcriptionally. The influence of miRNAs on the clinical manifestations of SCA has been little explored to date. Thus, this study aims to determine the expression profile of miRNAs that are involved in the inflammatory response in monocytes of adult SCA patients followed up regularly at the Hemope, with and without leg ulcers, and in monocytes of health controls; investigate whether these miRNAs correlate to this clinical manifestation; and evaluating the expression profile of genes associated to oxidative stress in reticulocytes of these individuals. Moreover, the influence of anti-inflammatory drugs will be investigated in THP-1 cells culture on the expression of miRNAs differentially expressed. The expression profile of miRNAs and genes associated to oxidative stress are going to be evaluated by PCR-Array, the results will be validated by quantitative real time PCR (qPCR). The influence of anti-inflammatory drugs will be evaluated by qPCR and appropriate protein analysis, after in silico analysis.