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 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.
Melenhorst
W B W H
WB
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands. w.b.w.h.melenhorst@path.umcg.nl
van den Heuvel
M C
MC
Stegeman
C A
CA
van der Leij
J
J
Huitema
S
S
van den Berg
A
A
van Goor
H
H
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009401:Nephrosis / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics; D014184:Transplantation, Homologous / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; D012333:RNA, Messenger; D051722:ADAM Proteins; C411902:ADAM19 protein, human