The glycocalyx covers the luminal surface of vascular endothelial cells and is injured in sepsis, leading to acute organ failure. However, there is no treatment option for endothelial glycocalyx injury at the moment. The immunoglobulin N-glycans have various biological roles. We have reported that the biantennary asialoglycan (G2) of serum immunoglobulin might have a protective role in endothelial glycocalyx injury in urosepsis. In this research, we will develop a novel therapeutic G2-rich immunoglobulin for the protection of endothelial glycocalyx injury. 
Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan of the extracellular matrix and present in the endothelial glycocalyx covering the apical surface of endothelial cells. We have demonstrated that transmembrane protein 2 (TMEM2) is a hyaluronidase that cleaves extracellular high-molecular-weight HA into intermediate-size fragments and essential for systemic HA catabolism and turnover, acting primarily on the surface of endothelial cells. We hypothesize that HA catabolism is a key in the endothelial glycocalyx disruption process and the inhibition of TMEM2 may protect the endothelial glycocalyx. In this research, we will develop compounds that inhibit HA catabolism of TMEM2 for endothelial glycocalyx injury.