Acute tubular necrosis induced by aminoglycoside-antibiotics is followed by a regenerative process which leads to the restoration of damaged tubules. It is well known that tubular regeneration is smediated by polypeptide growth factors such as
epidermal
growth factor (EGF). In the absence of nephrotoxic alterations, EGF is immunologcalized in distal tubules, whereas epidermal growth factor receptor (EGFR) immunostaining is localized in proximal tubules. After acute tubular necrosis, the sign of
regeneration is accompanied by redistribution of EGF immunoreactivity from distal to proximal tubudles and a reduction of total immunoreactive ECF due to a decrease of tissue-bound proEGF. However, it is controversial whether EGFR is downor
up-regulajted during this regenerative process.
We evaluated the time course of the regenerative response subsequent to tubular damage induced by aminoglycoside, with a particulajr attention paid to EGFR in order to examine whether it is down-or up-regulajted. Female Sprague-Dawley rats were
treated
during 4 and 8 consecutive days with a daily dose of 80 mg/kg gentanlicin i.p. Groups of experimental animals (n=10) were terminated at increasing time intervals (5, 9. 12. 16 days) after cessation of treatment. One hour before sacrifice each
individual
received i.p. 200mg/kg BrdU for. The immunonistochemical demonstration of cell proliferation (S-phase cell). Blood was collected at the time of sacrifice ot measure serum creatinine and BUN levels. EGFR immunoreactivity was r4evealed on
paraffin-embedded tissue section by immunohistochemical staining using polyclonal anti-EGFR antibody. Upon immunostaining sections in control kidneys, immunoreactive EGFRs exhibited a quite specific and restricted distrubution since they were
confined
to proxismal tubulejs. But proximal tubules undergoing fregenerative repair were characterized by a disappearance of EGFR, which expressed BrdU in immunohistochemical sections for BrdU. Beyond the episode of tubular regeneration, proximal tubules
recovered immunoreactive EGFR.
The results suggest that the apparent loss of EGFR could be due to a process of receptor down-regulation in proximal tubules displaying evidence of regenerative response.
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