Análise Morfológica e Funcional da Integrina Beta 2 (CD18)durante o desenvolvimento cardíaco

Abstract

Adhesion receptors play a key role in a variety of functions during embryonic development and after birth. Among such functions are processes involving morphogenesis, cellular adhesion, migration and differentiation. Among the several types of adhesion receptors are the integrins, which are the major family of surface receptors that mediate attachment of cells to the extracellular matrix. Integrins are transmembrane proteins that bind to proteins contained in intracellular complexes which are linked to the cytoskeleton. Integrins form heterodimers composed of one alpha and one beta subunit and, presently, 24 different heterodimers are known. Within the integrin family there is a subfamily which contains beta 2 integrin (CD18) in conjunction with one of several different types of alpha subunits. This subfamily has been reported to be primarily expressed on the surface of leukocytes, where it mediates adhesion to endothelial cells during leukocyte transmigration. The gene that encodes beta 2 integrin is localized on chromosome 21. Down syndrome patients, who have an extra copy of chromosome 21, display a reduction of mature lymphocytes and also an increased expression of beta 2 integrin. In addition, approximately 40% of Down syndrome patients have congenital heart defects, most commonly atrioventricular valve and septal malformations. During atrioventricular valve morphogenesis, a subset of endothelial cells within embryonic heart transforms into mesenchyme (epithelial-mesenchymal transformation), migrates into the cardiac jelly, and is responsible for the synthesis of connective tissue of the cardiac valves and the membranous portion of interventricular septum. Interestingly, research results obtained during my M.A. project using immunohistochemical methods indicated that beta 2 integrin is present not only in leukocytes, but also in the forming valves as well as in the myocardium and epicardium during cardiogenesis. Therefore, the objective of this work is to further characterize and verify the expression of beta 2 integrin, and then study its function during cardiogenesis. Data obtained using in situ hybridization techniques and PCR analysis confirmed that beta 2 integrin is present during cardiogenesis. Functional studies showed that beta 2 integrin plays a role during epithelial-mesenchymal transformation, affecting cellular migration. These observations support our hypothesis that beta 2 integrin is important for cardiac valve formation during cardiogenesis.