RENAL TISSUE EXPRESSION OF EGF AND EGF RECEPTOR AFTER ISCHEMIC TUBULAR INJURY - AN IMMUNOHISTOCHEMICAL STUDY

Rat kidneys undergoing tubular regeneration after ischaemic injury hav e been examined with regard to EGF, EGF receptor and vimentin, using i mmunohis necrosis tochemical techniques. Renal ischaemia was induced i n male Sprague-Dawley Rat kidneys undergoing tubular regeneration afte r ischaemic injury have been rats by 35-min clamping of renal arteries . Groups (n = 4-6) of experimental animals were killed at different ti me intervals (12, 24, 48, 72 h, 7 and 14 days) after reperfusion. One hour before sacrifice, each rat received i.p. 200 mg/kg 5-bromo-2'-deo xyuridine (BrdU) for the immunocytological demonstration of DNA synthe sis. Renal necropsies were processed to reveal by immunohistochemistry EGF, EGF receptor, vimentin, and BrdU incorporated into DNA of S-phas e cells. Tubular necrosis particularly involved proximal straight tubu les in the outer stripe of the outer medulla and was followed by tubul ar regeneration, with a peak of cell proliferation at 48-72 h and an a pparent dedifferentiation of tubular epithelium. As soon as 12 h after ischaemia, there was a substantial reduction of EGF immunostaining an d the incidence of distal tubules showing EGF immunoreactivity reached a nadir at 48 h. In control kidneys, EGF receptor was mostly immunolo calized in proximal tubules although juxtaglomerular cells also exhibi ted immunolabelling. EGF receptor immunostaining in tubular epithelium showed no major change during the episode of tubular necrosis (12-24 h) but disappeared in tubular profiles undergoing regenerative hyperpl asia(48-72 h). No vimentin immunostaining was found in tubules of cont rol kidneys. Tubular epithelium remained mostly vimentin negative duri ng the early phase of tubular necrosis/regeneration (12-72 h). By cont rast, 7 days after ischaemia numerous dedifferentiated tubules express ed vimentin. In conclusion, tubular regeneration after ischaemia is as sociated with a typical sequence of transient events: (1) reduction of EGF immunostaining; (2) disappearance of EGF receptors during the mit ogenic response; (3) expression of vimentin in tubular epithelium, and (4) return to a normal appearance.