Our data show that different macroscopic compartments of the renal lobe show distinct and reproducible patterns of gene expression. Each of the compartments that we dissected showed a highly characteristic pattern of gene expression that was consistent in these samples. Although paired samples from the same patient were more similar in their expression than samples from different patients, the variation in gene expression in each compartment between samples from different individuals was far less than we have observed for renal tumors of a given diagnostic class (Higgins et al., 2003
). This consistency of gene expression profiles characteristic of each region or substructure of the kidney is demonstrated through the tight grouping of similar samples through hierarchical clustering.
By examining the different anatomical subcompartments of the kidney, our study expands upon that of Yano et al.
), who have previously reported a microarray analysis of gene expression in nine samples of the adult renal cortex. In their analysis of 18,326 genes, they found some results similar to ours, in that genes encoding ion channels/transport proteins were highly expressed in their samples. Furthermore, metallothionein genes were highly expressed in the cortex in both their study and in ours. However, in contrast to the Yano group, we found higher-level expression of ribosomal genes in our medullary samples than in our cortex samples. Our data add a comprehensive profile of genes expressed in the medulla, papillary tips, and renal pelvis and permit a comparison of gene expression in cortex with other compartments of the kidney. Our inclusion of isolated glomeruli may prove particularly useful since genes in this cluster may be associated with genetic and immunologic glomerular diseases unique to the kidney.
Our attempt to categorize gene expression in the normal nephron via gross dissection of the renal lobe has some limitations. Some functionally distinct boundaries in the nephron are too small to permit gross dissection. The nephron takes a tortuous course through the renal lobe such that the proximal and distal convoluted tubules of the nephron are both located in the cortex. Furthermore, the normal kidney is composed of a variety of cell types other than the epithelium of the nephron. Thus, genes identified as expressed in the cortex may be expressed in the tubular epithelium, in the several different cell types of the glomeruli, in the peritubular capillaries or larger vessels, in the normal resident cells of the interstitium (Lemley and Kriz, 1991
), or in infiltrating leukocytes or dendritic cells.
Despite these limitations, the power of DNA microarray technology for discovery of genes relevant to renal physiology and pathology is readily apparent on inspection of the genes that comprise the individual clusters. For example, the glomerular cluster contains 196 genes and includes GLEPP1, ZO-1, actinin alpha 4, and osteonectin, all genes known to be expressed in the glomerulus and some documented to be involved in glomerulonephropathies. The “rediscovery” of these important genes using this technique indicates that many of the uncharacterized genes in this cluster will prove relevant to normal glomerular function or to glomerular diseases. One novel candidate gene is ficolin 3 (Hakata antigen) against which lupus patients' sera react, but expression of which has only been described in the liver and lung. Perhaps the most interesting discoveries to come from our microarray experiments are of renal expression of panels of apparently related but unexpected genes. The expression of detoxification genes in the renal cortex, of bile metabolism genes in the papillary tips, of genes involved in intestinal mucosal defense in the medulla suggests that the kidney may play a role in biological processes that were previously thought to be the exclusive domain of other organs. Alternatively, it may be that in the kidney these genes underlie functions other than those that have been previously recognized in other organs.