Increased expression of TGF-beta1 but not of its receptors contributes to human obstructive nephropathy

Abstract

Increased expression of TGF-beta1 but not of its receptors contributes to human obstructive nephropathy.

Background: Previous studies have revealed an increased expression of transforming growth factor-beta1 (TGF-beta1) and deposition of extracellular matrix in the kidney of animals with ureteral obstruction. However, these relationships have not been elucidated in the hydronephrotic kidney of humans.

Methods: We analyzed the tissue expression of extracellular matrix proteins, TGF-beta1, and its receptors in the human kidney with ureteral obstruction by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Obstructed kidneys (OBKs) were obtained from patients with ureteral tumors. A kidney specimen from patients with a renal tumor was used as control (CNKs).

Results: The interstitial volume was significantly increased in OBKs in comparison with CNKs. OBKs showed increased deposition of collagen types I and IV and fibronectin in the renal interstitium. RT-PCR revealed overexpression of collagen alpha1(IV) mRNA and fibronectin mRNA in OBKs. OBKs showed a significantly increased mRNA expression of TGF-beta1 in comparison with CNKs. The immunoreactivity for TGF-beta1 increased markedly in the interstitium of OBKs. There was a significant correlation between the TGF-beta1 mRNA level and the interstitial volume. However, there was no significant difference between OBKs and CNKs in the relative mRNA level nor in immunoreactivity for TGF-beta receptors.

Conclusions: These data suggest that TGF-beta1 may contribute to the interstitial fibrosis found in the human kidney with ureteral obstruction, mainly because of an increase in the expression of this cytokine without significant changes to its receptors.