GLOMERULAR EPITHELIAL CELL PROTEIN 1 IN INFLAMMATION, INJURY AND DEVELOPMENT

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Treatment of most forms of glomerular diseases remain relatively ineffective. To improve outcome and divise more effective treatment strategies we need to understand the structure and function of the glomerulus in molecular rather than purely physiologic and general anatomic terms. What are the molecules that constitute the delicate filtration mechanism of the glomerulus? How do they fit together? What happens to these molecules that causes the filtration surface to change shape and begin to leak proteins into the urinary space? How is the synthesis and distribution of these molecules regulated? At present, surprisingly, we have the answers to very few of these questions. We must find these answers if we are to take the next steps forward. The focus of this application therefore is to clone, sequence and begin to determine the role of a novel protein we have identified which is present only on the glomerular epithelial cell, and nowhere else in the body. Because of this unique location, and because the protein disappears when the glomerular epithelial cell is injured, we think that this protein could play an important role in maintaining the exquisitely delicate structure and incredible filtration characteristics of the glomerular filter. We will obtain the DNA sequence of this molecule which we call GLEPP1. We will go on to purify the protein, define the protein structure, and then make antibodies against it so that we can examine kidneys of people with diseases effecting the glomerular epithelial cell to see if GLEPP1 is absent or abnormally distributed in these people. We will look at the developing kidney to see when and where this protein first appears, and we will examine animal models of glomerular injury to see what happen to GLEPP1. We hope that GLEPP1 will be a tool that can show us how molecules in the glomerular filter are regulated, or even perhaps prove to be a key target protein that can help explain some glomerular diseases.