MicroRNAs expression profile and their influence on asthma experimental model in sickle cell transgenic mice

• Grant number: 16/13224-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2017
• End date: May 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Carla Fernanda Franco Penteado
• Grantee: Ana Carolina Borges Monteiro Padilha
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches, AP.TEM

Abstract

The inflammatory process in sickle cell anemia can be more widely investigated using mice that express human genes of ² globin. Using these animal models, it was demonstrated in vivo that both the adhesion of leukocytes to the endothelium as well as the leukocyte adhesion to sickled cells play a direct role in the vaso-occlusion process and suggest that the endothelium activation and the inflammatory response are required for leukocytes adherence and consequent vaso-occlusion. The systemic administration of lipopolysaccharide (LPS) and allergic asthma model by ovalbumin (OVA) in sickle cell anemia transgenic mice results in an exacerbated inflammatory response with increased expression in adhesion molecules and cytokines into the lung tissue. The microRNAs (miRNAs) belong to a class of regulatory RNAs, important in several biological processes. Studies have shown that miRNAs are selectively expressed in the cells of the immune system, suggesting an important role of miRNAs in regulating maturation, proliferation, differentiation and activation of these cells. MiRNAs can act both in innate and adaptive immune response, being the expression of miRNAS associated with signaling pathways and receptors. MiRNAs are considered promising candidates for new therapeutic approaches and also as biomarkers of diseases such as cancer, heart disease and chronic inflammatory diseases of the skin and lungs. Pulmonary complications are one of the leading causes of morbidity and mortality in sickle-cell disease, this study aims to evaluate the profile of miRNAs expression related to inflammatory response in the lungs of sickle cell anemia transgenic mice, subjected to allergic asthma model (OVA). The results may contribute to a better understanding of the mechanisms involved in the pathophysiology of pulmonary complications in sickle cell anemia. (AU)