Prostaglandins (PGs), including prostacyclin, and thromboxane (TX) have been detected in many tissues and body fluids. They differ widely in their biological activities. The most important of their effects include mediation of the reactivity of vascular and nonvascular smooth muscle, platelet aggregation, and tissue inflammation. In the kidney they modulate renal and glomerular blood flow, salt and water excretion, and some components of the renal inflammatory response. Because of the importance of PGs in regulating kidney function, we ask the following question: To what extent can substrate manipulation alter glomerular PG production and thereby modify renal function? To address this question we plan the following: 1. Using cultured glomerular mesangial and epithelial cells, we will determine incorporation and metabolism of three polyunsaturated fatty acids: arachidonic acid (AA), eicosapentaenoic acid (EPA) and dihomogammalinolenic acid (DHG). These are the substrates for synthesis of the """"""""1,"""""""" """"""""2"""""""" and """"""""3"""""""" series PGs respectively. 2. We will determine the relationship between fatty acid incorporation, PG production, and the contractile response of the whole glomerulus and cultured mesangial cells to agents such as angiotensin II (ANG II) and vasopressin (AVP). Mesangial cell proliferation and phagocytosis, as well as inflammation, will also be studied as a function of fatty acid incorporation. 3. Finally, we will determine the effect of dietary fatty acid manipulation in several models of renal disease.
| Johnson, Ali C M; Yabu, Julie M; Hanson, Sherry et al. (2003) Experimental glomerulopathy alters renal cortical cholesterol, SR-B1, ABCA1, and HMG CoA reductase expression. Am J Pathol 162:283-91 |
| Scharschmidt, L A; Gibbons, N B; Neuwirth, R (1989) Eicosapentaenoic and dihomo gamma linolenic acid metabolism by cultured rat mesangial cells. Am J Physiol 256:C101-8 |
