Extracellular matrix-related genes in kidney following ischemic
injury: potential role for tgf-[beta] in repair.
Basile, David P., 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 5:0154F, 1998.
The renal expression of TGF-[beta]1 is enhanced following induction of
ischemic injury in rat. In cultured renal cells, TGF-[beta]
stimulates the synthesis of extracellular matrix. To link TGF-[beta]1
expression with the regulation of extracellular matrix post-ischemia,
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), collagen IV-1 and fibronectin-EIIIA mRNAs were
significantly enhanced in kidneys within 12 hours to 3 days after
injury and remained elevated at 7-28 days post-ischemia 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 post
-ischemic injury. Collagen IV-1 and FN-EIIIA mRNAs were expressed
primarily in regenerating proximal tubules cells. Immunoreactivity
for FN-EIIIA was enhanced in the tubular basement membrane (TBM) of
regenerating proximal tubules and Collagen IV-1 immunoreactivity was
detected in thickened tubulointerstitial spaces. In contrast, TIMP-1
immunoreactivity was enhanced in distal nephron structures post
-ischemia. Immunoneutralization of TGF-[beta] in vivo attenuated the
increases in FN-EIIIA, collagen IV-l, PAI-1 and TIMP-1 mRNAs by 52%,
73%, 43% and 27%, respectively. These data are consistent with TGF
-[beta] expression post-ischemic injury participating in renal
regeneration of ECM homeostasis in the proximal TBM.
Received 3 June 1998; accepted in final form 3 September 1998.
APS Manuscript Number F141-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998