Altered epidermal growth factor expression and thyroxine metabolism
in kidneys following acute ischemic injury in rat.
Rogers, Sharon A., Steven B. Miller, and Marc R. Hammerman.
George M. O'Brien Kidney and Urological Disease Center, Renal
Division, Departments of Medicine and Cell Biology and Physiology,
Washington University School of Medicine, St. Louis MO 63110
APStracts 2:0103F, 1995.
To define the relationship between renal epidermal growth factor (EGF)
expression and thyroid hormones in acute renal failure, we performed
an analysis of the renal thyroid hormone-EGF axis following acute
ischemic renal injury in rats. Levels of mature EGF extractable from
kidney were elevated 24 hours post-injury and levels of membrane
-associated EGF-precursor reduced. Administration of triiodothyroinine
(T3) to rats either prior to or immediately following the induction
of injury, did not further increase levels of extractable EGF. Levels
of EGF mRNA in kidneys were reduced 24 hours following acute ischemic
damage, and not affected by administration of T3. Enhanced production
of mature EGF from EGF-precursor occurred in membranes isolated from
kidneys of rats 24 hours post-injury compared to production in
membranes from kidneys of normal rats. In addition, levels of
thyroxine 5'deiodinase activity in renal membranes were increased 24
hours following injury. Levels of circulating total T4, free T4 and
free T3 were reduced post-ischemic injury. Total T3 was unchanged.
The administration of T3 to normal rats increased renal 5'deiodinase
activity and EGF-precursor cleavage. Administration of
propylthiouracil to rats inhibited renal 5'deiodinase activity and
prevented the increase in extractable EGF post-ischemic injury. We
conclude that the increase in levels of mature EGF extractable from
kidneys of rats post-ischemic injury results from enhanced activity
of the serine protease that cleaves the EGF-precursor. This activity
may be stimulated by T3 produced in kidney. These alterations in
renal thyroxine metabolism and EGF expression could serve to
facilitate recovery of renal function following ischemia.
Received 19 January 1995; accepted in final form 1 June 1995.
APS Manuscript Number F14-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.