Increased transforming growth factor-beta 1 expression in regenerating rat renal tubules following ischemic injury.
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 h postinjury (1.5-fold vs. sham-operated controls), and by 24 h postinjury were elevated by 3.6-fold. Levels remained elevated for 14 days following ischemia, but were no longer elevated at 28 days postinjury. 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 postischemia, levels of TGF-beta 1 mRNA were elevated in the outer medulla only in tubules that 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 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.
Basile
D P
DP
George M. O'Brien Kidney and Urological Disease Center, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Rovak
J M
JM
Martin
D R
DR
Hammerman
M R
MR
D000818:Animals; D017403:In Situ Hybridization; D007511:Ischemia / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta