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 e xpression of active and latent TGF-beta peptide at various times durin g recovery from acute ischemic injury in rat. Levels of whole kidney T GF-beta 1 mRNA were elevated significantly at 12 h postinjury (1.5-fol d vs. sham-operated controls), and by 24 h postinjury were elevated by 3.6-fold. Levels remained elevated for 14 days following ischemia, bu t 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 medul la. When examined at 14 days postischemia, levels of TGF-beta 1 mRNA w ere elevated in the outer medulla only in tubules that appeared incomp letely regenerated. Immunohistochemical staining localized active TGF- beta to the lumen of proximal tubules in control animals and in desqua mated and regenerating tubular epithelial cells following ischemia. TG F-beta 1 latency-associated peptide was present intracellularly in pro ximal tubules of sham-operated rats and reduced following ischemia. We hypothesize that endogenous renal TGF-beta serves to promote tissue r egeneration following acute injury via an autocrine or paracrine mecha nism.