Roles of the core protein of Syndecan-4 and heparan sulfate chains in endothelial cells signaling pathways

Abstract

Glycoconjugates, including proteoglycans, belong to the most abundant class of structurally diverse and heterogeneous molecules present in the extracellular matrix (ECM) and on the cell surface. Syndecan-4 (Syn4), a transmembrane proteoglycan, plays an important role in cellular behavior, due to its interaction with the cytoskeleton through the protein core and the extracellular space via heparan sulfate (HS) chains. These molecules physically communicate the ECM to the cytoskeleton, acting as signal transducer from the extracellular medium to the intracellular environment and vice versa. Due to this property, a myriad of cellular functions can be affected, such as: cell differentiation, proliferation, migration, apoptosis and inflammatory response. The present project aims to establish the molecular basis of possible functional complexes among proteoglycans / integrins / cellular receptors and MEC components in cell dynamics using molecular and cellular biology tools. Previous results show that the knockdown of Syn4 up regulates the expression of C-Myc, C-Myb and EBF2 transcription factor and downregulates microRNA204 expression. Also, Syn4 knockdown cells show less amounts of Cav1 and lower expression of Cav1 mRNA. The present proposal aims to elucidate how some transcription factors and microRNAs participate in syndecan-4 signaling transduction. This project also points to the use of the already constructed libraries as well as to develop new libraries using endothelial cells and interested genes which are related to our model of interest.