Increased transforming growth factor-[beta]1 expression in
regenerating rat renal tubules following ischemic injury.
Basile, David P., Jason M. Rovak, Daniel R. Martin, 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 2:0193F, 1995.
To gain insight into the role that transforming growth factor-[beta]1
(TGF-[beta]1) plays in the regeneration of kidneys following acute
renal failure, we characterized the expression of TGF-[beta]1 mRNA
and the expression of active and latent TGF-[beta] peptide at various
times during recovery from acute ischemic injury in rat. Levels of
whole kidney TGF-[beta]1 mRNA were elevated significantly at 12 hours
post-injury (1.5 fold vs. sham-operated controls) and by 24 hours
post-injury were elevated by 3.6 fold. Levels remained elevated for
14 days following ischemia, but were no longer elevated at 28 days
post-injury. In situ hybridization demonstrated that the elevated
expression of TGF-[beta]1 was localized predominantly to cells in the
regenerating tubules in the outer medulla. When examined at 14 days
post-ischemia, levels of TGF-[beta]1 mRNA were elevated in the outer
medulla only in tubules which appeared incompletely regenerated.
Immunohistochemical staining localized active TGF-[beta] to the lumen
of proximal tubules in control animals and in desquamated and
regenerating tubular epithelial cells following ischemia. TGF-[beta]1
latency-associated peptide (LAP) was present intracellularly in
proximal tubules of sham-operated rats and reduced following
ischemia. We hypothesize that endogenous renal TGF-[beta] serves to
promote tissue regeneration following acute injury via an autocrine
or paracrine mechanism.
Received 8 August 1995; accepted in final form 23 October 1995.
APS Manuscript Number F264-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95