CHAPTER 3
Improvement of heparan sulfate expression in the skin basement membrane after kidney and pancreas- kidney transplantation*
Johan W. van der Pijl1 Mohamed R. Daha1 Nicole A.M. Verhagen1 Jacob van den Born2 Richard Bucala3 Jo H. M. Berden2 Leendert A. van Es1
Department of Nephrology (1) Leiden University Medical Center, Department of Nephrology (2) University of Nijmegen, and The Picower Institute for Medical Research (3) Manhasset, New York, USA
*Submitted
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Abstract
The amount of the immunoreactive glycosaminoglycan side chains of heparan sulfate proteoglycan in the basement membranes of glomeruli and skin is decreased in patients with renal failure.
We designed this prospective study to evaluate the extracellular matrix of the skin basement membrane of fourteen patients with type 1 diabetes mellitus before and after successful pancreas-kidney transplantation and of nine patients with non-diabetic renal failure before and after successful kidney transplantation. Monoclonal antibodies directed against the heparan sulfate polysaccharide side chain (JM-403) and against the core protein of the glomerular heparan sulfate proteoglycan agrin (JM-72), together with a monoclonal antibody against advanced glycosylation end products (4G9), and a polyclonal antibody against collagen type I were used for this immunohistochemical study.
Using semiquantative scoring, we found a low expression of the JM-403 heparan sulfate epitope in the skin basement membrane in patients with renal failure, while the expression increased significantly after transplantation (P = 0.02). Neither the staining scores for the core protein of heparan sulfate proteoglycan (P = 0.70) nor the staining scores for collagen type I (P = 0.72) changed. The high staining scores for advanced glycosylation end products before transplantation regressed significantly after transplantation (P <
0.02).
Our findings suggest that the changes in the composition of heparan sulfate in extra-renal basement membranes are reversible, since the altered skin basement membrane extracellular matrix of patients with non-diabetic or diabetic renal failure normalises after successful kidney or pancreas-kidney transplantation.
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