Upregulation of ADAM19 in Chronic Allograft Nephropathy

ADAM19 (a disintegrin and metalloproteinase 19) is involved in cell–cell and cell‐matrix interactions and tumor necrosis factor (TNF)‐alpha shedding. We studied ADAM19 in chronic allograft nephropathy (CAN) nephrectomies and in normal human kidneys. Reverse transcriptase (RT) PCR revealed an upregul...

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Bibliographic Details
Published in:American journal of transplantation 2006-07, Vol.6 (7), p.1673-1681
Main Authors: Melenhorst, W. B. W. H., Van Den Heuvel, M. C., Stegeman, C. A., Van Der Leij, J., Huitema, S., Van Den Berg, A., Van Goor, H.
Format: Article
Language:English
Subjects:
ADAM
ADAM Proteins - genetics
ADAM Proteins - metabolism
ADAM19
Adolescent
Adult
Aged
allograft nephropathy
Biological and medical sciences
Biomarkers
Biopsy
Chronic Disease
Female
Graft Rejection - metabolism
Graft Rejection - pathology
Humans
interstitial fibrosis
Kidney Transplantation
Male
Medical sciences
meltrin beta
metalloproteinase
Middle Aged
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Nephrosis - metabolism
Nephrosis - pathology
Nephrosis - surgery
Renal failure
RNA, Messenger - genetics
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Transplantation, Homologous - pathology
Up-Regulation - genetics
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Summary:ADAM19 (a disintegrin and metalloproteinase 19) is involved in cell–cell and cell‐matrix interactions and tumor necrosis factor (TNF)‐alpha shedding. We studied ADAM19 in chronic allograft nephropathy (CAN) nephrectomies and in normal human kidneys. Reverse transcriptase (RT) PCR revealed an upregulation of ADAM19 mRNA in CAN when compared with control kidneys (p = 0.002). Using RNA in situ hybridization (ISH), we detected moderate ADAM19 mRNA expression in vascular smooth muscle cells (SMCs) and distal tubuli of control kidneys. In CAN, massive ADAM19 expression was detected in SMCs, distal tubuli, glomerular sclerotic lesions and inflammatory CD4+ cells. To determine whether ADAM19 is specifically related to CAN, we studied transplant biopsies with and without CAN, acute rejection and non‐transplant‐related kidney diseases: interstitial fibrosis (IF), interstitial atrophy, glomerular fibrosis and interstitial inflammation. In various renal structures, ADAM19 mRNA was significantly higher in CAN when compared with renal allografts without CAN or acute rejection. ADAM19 expression in renal endothelium was significantly higher in acute rejection when compared with renal allografts without CAN. When compared to CAN, ADAM19 was expressed to a similar extent in non‐transplant‐related interstitial and glomerular fibrosis, interstitial atrophy and inflammation. Although these observational data do not establish a cause and effect relationship, ADAM19 may have a modulatory role in the dysfunctional renal allograft state. ADAM19, a disintegrin and metalloproteinase involved in cell‐cell and cell‐matrix interactions was strongly expressed in kidney allografts with fibrosis and atrophy (CAN), suggesting a role in these damaged kidneys.
ISSN:1600-6135
1600-6143
DOI:10.1111/j.1600-6143.2006.01384.x