Epidermal growth factor accelerates functional recovery from ischaemic acute tubular necrosis in the rat: role of the epidermal growth factor receptor.
1. Severe, ischaemic, acute tubular necrosis was induced in rats by bilateral occlusion of the renal arteries. The experimental group received exogenous epidermal growth factor infused directly into the renal arterial circulation. Serum creatinine concentration was measured daily for 1 week. Epidermal growth factor receptor binding was measured by autoradiography of whole kidney sections. Renal cell proliferation was measured by incorporation of [3H]thymidine into DNA. 2. Serum creatinine concentration increased after acute tubular necrosis with a peak at 48 h and remained elevated above control levels after 7 days. Binding of radiolabelled epidermal growth factor occurred in all regions of the kidney 48 h after ischaemia. Treatment with exogenous epidermal growth factor attenuated the rise in serum creatinine by 4 days after acute tubular necrosis and after 7 days serum creatinine was lower than in animals that did not receive epidermal growth factor. Infusion of epidermal growth factor also increased renal DNA synthesis. 3. The increase in epidermal growth factor binding in the kidney after acute tubular necrosis and the attenuation of the increase in serum creatinine concentration by administration of exogenous epidermal growth factor, suggest a role for epidermal growth factor in recovery from ischaemic damage. The increase in DNA synthesis in response to epidermal growth factor indicates that its effect may be due, at least in part, to accelerated tubular cell proliferation.
Norman
J
J
Department of Medicine, UCLA School of Medicine 90024.
Tsau
Y K
YK
Bacay
A
A
Fine
L G
LG
D058186:Acute Kidney Injury / Q000188:drug therapy*; D000818:Animals; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007683:Kidney Tubular Necrosis, Acute / Q000097:blood / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D004815:Epidermal Growth Factor; D004247:DNA; D003404:Creatinine; D066246:ErbB Receptors; D013936:Thymidine