EXPRESSION OF TISSUE KALLIKREIN IN HUMAN KIDNEY

1. We studied the distribution of human tissue kallikrein mRNA in norm al and diseased kidney, using in situ hybridization, together with imm unohistochemical localization of renal kallikrein protein. Materials s tudied were (a) normal tissue from kidneys removed because of localize d renal carcinoma, (b) kidneys removed because of post-traumatic haemo rrhage and (c) renal biopsy specimens from patients with membranous gl omerulonephritis and nephrotic syndrome. 2. A 1.35kb EcoRI fragment of human tissue kallikrein cDNA was labelled with [P-32]dCTP using the r andom-primer technique, and used for in situ hybridization. A specific rabbit antibody to active human urinary kallikrein was employed for i mmunocytochemistry, using a peroxidase-antiperoxidase method. 3. By in situ hybridization, no tissue kallikrein gene expression was seen in the carcinoma nephrectomy specimens. Positive expression was seen in t he trauma nephrectomy tissue, and in four of five nephrotic syndrome b iopsies. In all kidneys, expression was confined to the renal cortex. The dominant site of gene expression was the distal tubule. Apart from one area of positive signal related to an epithelial cell of Bowman's capsule, expression was not observed in glomeruli. Expression was als o seen in the walls of large- and medium-sized blood vessels. 4. By im munohistochemistry, the dominant site of immunoreactivity was the dist al tubule. Dense staining was also seen in granular peripolar cells an d in isolated parietal epithelial cells close to the vascular pole. Is olated immunoreactive cells were seen in the media of large- and mediu m-sized arteries. 5. The tissue kallikrein gene in the kidney may not be constitutively expressed, but is expressed in response to physiolog ical or pathological stimuli. The dominant site of gene expression and tissue kallikrein localization is the distal tubule. Although kallikr ein is present in granular peripolar cells in human kidney, mRNA was n ot located at this site. It is possible that kallikrein in these cells derives from absorption from glomerular filtrate. Tissue kallikrein m RNA and protein are present in the walls of blood vessels in human kid ney. The significance of vascular kallikrein expression requires furth er investigation.