Gene Expression in the Normal Adult Human Kidney Assessed by Complementary DNA Microarray

Abstract

The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied gene expression in dissected renal lobes of five adult human kidneys using cDNA microarrays representing ϳ30,000 different human genes. Total RNA was isolated from sections of the inner and outer cortex, inner and outer medulla, papillary tips, and renal pelvis and from glomeruli isolated by sieving. The results revealed unique and highly distinctive patterns of gene expression for glomeruli, cortex, medulla, papillary tips, and pelvic samples. Immunohistochemical staining using selected antisera confirmed differential expression of several cognate proteins and provided histological localization of expression within the nephron. The distinctive patterns of gene expression in discrete portions of the kidney may serve as a resource for further understanding of renal physiology and the molecular and cellular organization of the nephron. INTRODUCTIONThe kidney is a multifunctional organ with critical roles in selective elimination of soluble wastes, acid base, electrolyte, and hormonal homeostasis, and regulation of blood pressure and erythropoiesis. The nephron, the functional unit of the kidney, is a highly ordered structure, consisting of several distinct specialized cell types. An ultrafiltrate of the blood, formed in the glomerulus traverses the nephron, where essential solutes are selectively reabsorbed, whereas wastes are concentrated and excreted. The diverse functions of the kidney are divided in a stereotyped manner among the cells of the nephron and associated structures. The specialization of function along the nephron is reflected in the gross anatomy of the renal lobe. The cortex contains glomeruli, the juxtaglomerular apparatus, and the proximal and distal convoluted tubules, where the plasma ultrafiltrate is formed and the majority of its components are reabsorbed, and the medulla contains the loop of Henle and collecting ducts, where the ultrafiltrate is concentrated.The characteristic pattern of functional specialization of cells along the length of the normal nephron should be accompanied by corresponding regional variation in gene expression patterns. Gene expression profiles of each segment could provide insight into the proteins and systems involved in the function of each portion of the nephron. A comprehensive view of gene expression would therefore contribute to an understanding of normal renal physiology and its derangement in renal disease. To further explore the genetic programs that underlie the function of the nephron, we have analyzed the gene expression patterns in isolated normal glomeruli and in ...

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