Transforming growth factor-β in acute renal failure: Receptor expression, effects on proliferation, cellularity, and vascularization after recovery from injury

Kimberly R. Spurgeon, Deborah L. Donohoe, David P. Basile

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Transforming growth factor (TGF)-β1 and a number of TGF-β-responsive genes are transiently enhanced following induction of ischemic acute renal failure (ARF) in the rat. The mRNA and protein expression of TGF-β receptors were analyzed in postischemic rat kidneys by ribonuclease protection, in situ hybridization, and immunohistochemistry. TGF-βRI and -RII were enhanced within 3 days of ischemia-reperfusion (I/R) injury and remained elevated for up 7 days post-I/R; TGF-β receptor expression was localized primarily in regenerating tubules within the outer medulla. A neutralizing TGF-β antibody exacerbated cellular proliferation observed on day 3 postischemia but had no effect on day 1 or 2. TGF-β antibody treatment had no measurable effect on loss of renal function or the restoration of renal function during the recovery response for up to 35 days postsurgery. However, ischemic injury resulted in modest renal hypertrophy that is due, in part, to in an increase in the number of interstitial cells in the postischemic kidney. Immunohistochemistry showed that several of these cells stained positively for the fibroblast-specific marker, S100A4 positive. Anti-TGF-β treatment substantially attenuated the renal hypertrophy, interstitial cellularity, and S100A4-positive cells present at 35 days post-I/R. Finally, TGF-β immunoneutralization attenuated the loss of renal vascular density following recovery from I/R injury. These data suggest that the TGF-β/TβR system is enhanced in the postischemic kidney. However, the current study failed to identify a prominent role for this system in the repair of proximal tubules following ARF. In contrast, the activation of this system may play an important role in the long-term structure of the postischemic kidney by influencing microvascular structure and interstitial cellularity.

Original languageEnglish (US)
Pages (from-to)F568-F577
JournalAmerican Journal of Physiology - Renal Physiology
Volume288
Issue number3 57-3
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

Keywords

  • Interstitial cellularity
  • Ischemia-reperfusion
  • Microvascular structure

ASJC Scopus subject areas

  • Physiology
  • Urology

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