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in acute renal failure: receptor expression, effects on proliferation, cellularity and vascularization after recovery from injury
1 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: dbasile{at}mcw.edu.
TGF-
1, and a number of TGF-
responsive genes are transiently enhanced following induction of ischemic acute renal failure in rat. The mRNA and protein expression of TGF-
receptors were analyzed in post-ischemic rat kidneys by ribonuclease protection, in situ
hybridization and immunohistochemistry. TGF-
RI and RII were enhanced within 3 days of I/R injury and remained elevated for up 7 days post-I/R; TGF-
receptor expression was localized primarily in regenerating tubules within the outer medulla. A neutralizing TGF-
antibody exacerbated cellular proliferation observed on day-3 post-ischemia, but had no effect on day 1 or
2. TGF-
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 post-surgery. 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 post-ischemic kidney. Immunohistochemistry showed that several of these cells stained positively for the fibroblast specific marker, S100A4- positive. Anti-TGF-
treatment substantially attenuated the renal hypertrophy, interstitial cellularity, and S100A4 positive cells present at 35 days post-I/R. Finally, TGF-
immunoneutralization attenuated the loss of renal vascular density following recovery from I/R injury. These data suggest that the TGF-
/ T
R system is enhanced in the post-ischemic 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 post-ischemic kidney by influencing microvascular structure and interstitial cellularity.
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