EXPRESSION OF EPIDERMAL GROWTH-FACTOR AND ITS RECEPTOR IN NORMAL AND DISEASED HUMAN KIDNEY - AN IMMUNOHISTOCHEMICAL AND IN-SITU HYBRIDIZATION STUDY

The kidney is one of the major sites of EGF production and there it se ems to play several biological functions, such as modulation of cell g rowth, renal repair following injury, regulation of Cellular;metabolis m and glomerular haemodinamics. The present study was first aimed al l ocalizing EGF and its receptor (R) in normal human kidney by immunohis tochemical and in situ hybridization techniques. Then, the distributio n of the growth factor and its R was explored in biopsy specimens from eight patients with acute tubulointerstitial damage. In the normal hu man kidney, both EGF immunoreactivity and EGF mRNA were localized in t ubular profiles corresponding to Henle's loop and, although to a lesse r intensity, to distal convoluted tubule. EGF immunostaining was remar kable mainly at the apical surface of tubular cells. EGF-R protein exp ression was detected in glomerular endothelial cells, in peritubular c apillaries and arteriolar walls, as well as along the thick ascending limb of Henle's loop and distal convoluted tubule, where it colocalize d with Tamm-Horsfall protein. Immunohistochemical analysis of tubular profiles revealed that EGF-R was located especially along the basolate ral membrane of tubular cells and within the basal part of cytoplasm. Endogenous alkaline phosphatase and CHIP28 positive tubules did not sh ow any signal for EGF and its receptor. Kidneys with acute tubulointer stitial injury exhibited a dramatic decrease of EGF expression, wherea s EGF-R showed only minor modifications. Interestingly, EGF-R was loca lized to both apical and antiluminal membranes of positive tubular cel ls. It is concluded that EGF-EGF receptor loop may be relevant in the pathogenesis of acute tubulointerstitial damage and recovery from tubu lar injury, while its role in the physiological renewal of the urothel ium remains speculative.