Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA
| Autor: | M. L. Nicholson, G R Bicknell, J R Waller |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Pathology medicine.medical_specialty Tenascin Matrix metalloproteinase Nephropathy Extracellular matrix Postoperative Complications Fibrosis medicine Humans Transplantation Homologous RNA Messenger Kidney Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinase-1 biology business.industry Reverse Transcriptase Polymerase Chain Reaction Biopsy Needle Tissue Inhibitor of Metalloproteinases Tissue inhibitor of metalloproteinase Middle Aged medicine.disease Immunohistochemistry Kidney Transplantation Matrix Metalloproteinases Transplantation medicine.anatomical_structure biology.protein Surgery Female Kidney Diseases business |
| Zdroj: | The British journal of surgery. 89(7) |
| ISSN: | 0007-1323 |
| Popis: | Background Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo-interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of extracellular matrix and the development of chronic renal allograft nephropathy in human renal transplants. Methods Forty renal allografts with stable renal function were biopsied 6 months after transplantation. Single glomeruli were plucked from the surface of these protocol biopsies and total messenger RNA (mRNA) was extracted. Reverse transcriptase–polymerase chain reaction was used to study the intragraft expression of several fibrosis-associated genes (collagen III, collagen IVα2, matrix metalloproteinase (MMP) 2, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, tenascin and transforming growth factor (TGF) β). The level of tubulo-interstitial fibrosis was measured by quantitative immunostaining of collagen III. Results There were positive correlations between the level of tubulo-interstitial collagen III immunostaining and intragraft expression of the genes for TIMP-1 (rs = 0·70, P < 0·02) and TIMP-2 (rs = 0·59, P < 0·02). Interstitial fibrosis was also strongly correlated with the levels of TGF-β mRNA (rs = 0·67, P < 0·002). Finally, TIMP-1 expression increased with TGF-β expression (rs = 0·77, P < 0·002). Conclusion Failure of extracellular matrix degradation may be an important molecular mechanism in the pathogenesis of chronic renal allograft damage. |
| Databáze: | OpenAIRE |
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