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- Title
Increased expression of TGF-β1 but not of its receptors contributes to human obstructive nephropathy.
- Authors
Kaneto, Hiroyuki; Ohtani, Haruo; Fukuzaki, Atsushi; Ishidoya, Shigeto; Takeda, Atsushi; Ogata, Yukihiko; Nagura, Hiroshi; Orikasa, Seiichi
- Abstract
Increased expression of TGF-β1 but not of its receptors contributes to human obstructive nephropathy. Background. Previous studies have revealed an increased expression of transforming growth factor-β1 (TGF-β1) 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-β1, 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 α1(IV) mRNA and fibronectin mRNA in OBKs. OBKs showed a significantly increased mRNA expression of TGF-β1 in comparison with CNKs. The immunoreactivity for TGF-β1 increased markedly in the interstitium of OBKs. There was a significant correlation between the TGF-β1 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-β receptors. Conclusions. These data suggest that TGF-β1 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.
- Subjects
TRANSFORMING growth factors; KIDNEY diseases; SECRETION
- Publication
Kidney International, 1999, Vol 56, Issue 6, p2137
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1999.00790.x