MicroRNAs expression profile and their influence on models of lung inflammation in sickle cell transgenic mice

• Grant number: 14/13198-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2015
• Effective date (End): December 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carla Fernanda Franco Penteado
• Grantee: Roger Barbosa Ferreira
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Sickle cell disease mouse models have allowed wider investigation of the inflammatory process in sickle cell anemia. Studies with these mice have demonstrated that both leukocyte adhesion to the endothelium and to sickled red blood cells play a direct role in the vaso-occlusive process and suggest that endothelial activation and inflammatory response are required for leukocyte adhesion and consequent vaso-occlusion. Systemic administration of lipopolysaccharide (LPS) and ovalbumin (OVA) allergic asthma model in transgenic sickle mice result in an exacerbated inflammatory response with increased expression of adhesion molecules and cytokines in lung tissue. In addition, previous results from our laboratory demonstrated that intranasal challenge with LPS results in augmented influx of leukocytes (primarily neutrophils), chemokines (KC and MIP-2), and TNF± into the BAL of Berkeley sickle mice when compared with control animals. MicroRNAs (miRNAs) belong to a regulatory class of RNAs with great importance in several biological processes. Studies demonstrated that miRNAs are selectively expressed in immune cells, suggesting an important role of miRNAs in the regulation of maturation, proliferation, differentiation and activation of these cells. miRNAs are involved in the development and fate of immune cells, and in both innate and adaptive immune responses, whereby strong evidence links miRNA expression to signalling pathways and receptors. miRNAs are also promising candidates for new, targeted therapeutic approaches and as biomarkers of disease, such as cancers, heart disease, and chronic inflammatory diseases of the skin and lungs. Since pulmonary complications are an important cause of morbidity and mortality in sickle cell disease, this study aims to evaluate the profile of miRNAs expression and their influence on genes involved to inflammatory response in the lungs of transgenic sickle cell mice subjected to two models of lung inflammation: acute pulmonary inflammation model (LPS) and allergic asthma model (OVA). The results will contribute to a better understanding of the mechanisms involved in pulmonary complications of sickle cell anemia.