Background
Epithelial and endothelial barriers are essential to life. While the endothelium lines the vasculature and ensures tissue supply with nutrients and oxygen, the epithelium forms the barrier between tissues and the outer environment thus protecting organs from invading harmful agents. Dysfunction in the epithelial or endothelial barrier underlies various diseases such as acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that affects over 190,600 people each year in the United States and accounts for 74,500 deaths. The injury of the alveolar epithelial and endothelial barriers is the hallmark of ARDS, which can be induced by several factors, including infection, aspiration syndromes, blood transfusion, and mechanical forces. While the damage and repair of the endothelial barrier are well-characterized, the mechanism of epithelial injury and repair is poorly understood. Current therapy relies on supportive care, rather than targeting the underlying pathophysiology of the disease. Thus, there is a need for agents and methods for improving epithelial and endothelial barrier function.
Technology Overview
Scientists at Rochester have developed a method of improving the integrity or function of an epithelial or endothelial barrier using gene therapy. The Na+, K+-ATPase (NKA), is an ion pump expressed in all mammalian cells, and it is well-known for its transport activity – moving Sodium (Na+) out of the cell and importing Potassium (K+). The NKA has been shown to play a critical role in the pathogenies of ARDS by affecting lung barrier integrity which results in accumulation of edema fluid leading to hypoxia. Increasing the gene expression of the NKA’s β1 subunit and protein kinase MRCKα confer protection to the alveolar epithelial barrier, as demonstrated by increased expression of tight junction proteins and decreased alveolar barrier permeability.
Benefits
Promising drug to enhance epithelial barrier function that could ultimately lead to pharmacological treatment of ARDS.
Applications