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NDT Advance Access published online on January 18, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfk076
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 24, 2005
Accepted December 22, 2005

Original Article

Effects of low molecular weight heparin in obstructed kidneys: decrease of collagen, fibronectin and TGF-{beta}, and increase of chondroitin/dermatan sulfate proteoglycans and macrophage infiltration

Inah M. D. Pecly 1, Rômulo G. Gonçalves 2, Ednei P. Rangel 2, Christina M. Takiya 3, Fernanda S. Taboada 1, Cesônia A. Martinusso 2, Mauro S. G. Pavão 1, and Maurilo Leite Jr 2 *

1 Laboratório de Tecido Conjuntivo, Instituto de Bioquímica Médica, Programa de Glicobiologia, Brazil
2 Serviço de Nefrologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho
3 Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil

* To whom correspondence should be addressed.
Maurilo Leite Jr, E-mail: mleitejr{at}hucff.ufrj.br



  Abstract

Background. Heparin exerts beneficial effects in different experimental models of nephropathy, as observed by the preservation of the structural morphology of the kidney after heparin therapy. Here we investigate molecular and cellular events involved in the protective effects of heparin in the progression of renal disease after unilateral ureteral obstruction.

Methods. Thirty-six rats were divided into six groups: group C (control) was not subjected to any surgical manipulation; group S (sham) was subjected to surgical manipulation but without ureteral ligation; group UUO was subjected to ureteral obstruction and received no treatment; group UUO + S was subjected to ureteral obstruction and received saline subcutaneously (s.c.) once daily; group UUO + H was subjected to ureteral obstruction and received low molecular weight heparin (LMW-Hep; 4 mg/kg) s.c. once daily; and group C + H was not subjected to any surgical manipulation and received LMW-Hep (4 mg/kg) s.c. once daily. After 14 days, the content of collagen, fibronectin, total glycosaminoglycans (GAGS), chondroitin sulfate/dermatan sulfate proteoglycans (CS/DSPGs), transforming groth factor-{beta} (TGF-{beta}) and cellular infiltration were determined in the kidneys by immunohistochemical and biochemical techniques.

Results. Collagen, fibronectin, total GAGS, CS/DSPGs, TGF-{beta} and cellular infiltration increased significantly in group UUO. LMW-Hep treatment reduced collagen, fibronectin and TGF-{beta}, but induced an increase in the content of total GAGS, CS/DSPGs and macrophage infiltration in group UUO + H when compared with group UUO.

Conclusions. LMW-Hep diminishes fibrosis in obstructed kidneys by downregulating the synthesis of collagen, fibronectin and TGF-{beta}. The mechanisms underlying the overproduction of CS/DSPGs and the increase in cellular infiltration upon LMW-Hep administration remain to be elucidated.

Keywords: animal model; collagen; glycosaminoglycans; low molecular weight heparin; unilateral ureteral obstruction.
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