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in repair
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, Missouri 63110
The renal expression of transforming growth factor-
1
(TGF-
1) is enhanced following induction of ischemic injury in rat. In cultured renal cells, TGF-
stimulates the synthesis of
extracellular matrix. To link TGF-
1 expression with the regulation
of extracellular matrix postischemia, we characterized the
expression of several genes known to regulate extracellular matrix
synthesis at various times during recovery from acute ischemic renal
injury in rat. Levels of mRNA for plasminogen activator inhibitor-1
(PAI-1), tissue inhibitor of metalloprotease-1 (TIMP-1),
1(IV) collagen, and fibronectin-EIIIA (FN-EIIIA) mRNAs were significantly enhanced in
kidneys within 12 h to 3 days after injury and remained elevated at
7-28 days postischemia relative to levels in kidneys of
sham-operated controls. PAI-1 mRNA and peptide were localized in
regenerating proximal tubules at 3 and 7 days postischemic injury.
1(IV) Collagen and FN-EIIIA
mRNAs were expressed primarily in regenerating proximal tubule cells.
Immunoreactivity for FN-EIIIA was enhanced in the tubular basement
membrane (TBM) of regenerating proximal tubules, and
1(IV) collagen immunoreactivity
was detected in thickened tubulointerstitial spaces. In contrast,
TIMP-1 immunoreactivity was enhanced in distal nephron structures
postischemia. Immunoneutralization of TGF-
in vivo
attenuated the increases in FN-EIIIA,
1(IV) collagen, PAI-1, and
TIMP-1 mRNAs by 52%, 73%, 43%, and 27%, respectively. These data
are consistent with TGF-
expression postischemic injury participating in renal regeneration of extracellular matrix homeostasis in the proximal TBM.
acute renal failure; differentiation; proximal tubule; regeneration; transforming growth factor-
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