Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of vascular cell adhesion molecule-1 (VCAM-1) in 11 human renal allograft biopsies and 3 normal kidney specimens was investigated by immunocytochemistry. VCAM-1 expression was correlated with the degree of CD3+ T cell infiltration and the clinicopathologic diagnosis of acute rejection. CD3+ infiltrates were seen in all biopsies with rejection, but not in normal biopsies or one with acute tubular necrosis, and were accompanied by CD68+ monocyte/macrophage infiltrates. In normal biopsies, VCAM-1 was present on occasional tubules, where its expression was patchy and restricted to the basolateral surface of cells with slight cytoplasmic staining. The total number of tubules expressing VCAM-1 significantly increased in specimens infiltrated with CD3+ T cells. Moreover, in these infiltrated biopsy specimens, VCAM-1 was present throughout the cytoplasm of tubular cells concentrated on the basolateral surface. VCAM-1 was also observed on vascular endothelial cells where its expression correlated with the degree of CD3+ infiltrate. Mean scores (0 to 3+) for endothelial VCAM-1 expression increased from 0 (CD3+ score, 0) to a mean score of 2.25 in association with CD3+ T cell infiltrates (CD3+ score, 3). Endothelial VCAM-1 was predominantly on vessels in areas of infiltrate, including peritubular capillaries, venules, and arterioles, but was notably absent on glomerular endothelium. VCAM-1 also stained mesangial cells in an occasional CD3+ infiltrated specimen. It was concluded that the expression of VCAM-1 is increased on renal tubules and renovascular endothelium in rejecting renal allografts in association with CD3+ infiltrates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of vascular cell adhesion molecule-1 in human renal allografts. 128 31

Expression of the cellular adhesion molecules ICAM-1, VCAM-1, E-selectin and PECAM in human kidney allografts was assessed by immunoperoxidase labelling of cryostat sections. Biopsies from 10 kidneys immediately prior to transplantation and 58 biopsies from 51 kidney transplants with graft dysfunction were studied. Allograft dysfunction was due to acute tubular necrosis (n = 5), acute rejection (n = 30), cyclosporin A (CyA) nephrotoxicity (n = 6), acute pyelonephritis (n = 3), recurrent glomerulonephritis (n = 4) and chronic rejection (n = 10). There was variability in the distribution of ICAM-1, VCAM-1 and E-selectin expression in pretransplant kidneys but the principal observation was a marked increase in the expression of ICAM-1 and VCAM-1 by the renal vasculature and the proximal tubules during acute rejection. By contrast, grafts with dysfunction not attributed to rejection showed a pattern of ICAM-1 and VCAM-1 expression similar to that observed prior to transplantation. E-selectin was expressed only weakly by occasional intertubular capillaries during acute rejection but the three grafts with pyelonephritis displayed strong expression of E-selectin on intertubular capillaries. There was no change in the pattern of PECAM expression following transplantation. The induction of ICAM-1 and VCAM-1 during rejection may contribute to the recruitment of mononuclear cells and render endothelial and tubular renal cells more susceptible to cell-mediated injury.
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PMID:Adhesion molecule expression (ICAM-1, VCAM-1, E-selectin and PECAM) in human kidney allografts. 752 37

Ischaemia followed by reperfusion (I/R) can induce inflammation and injury and is a risk factor for delayed graft function and rejection of transplanted kidneys. Inflammation is regulated by NF-kappaB transcription factors which induce pro-inflammatory molecules in endothelial cells (EC). We examined whether A20, a negative regulator of NF-kappaB, can protect kidneys from I/R injury. To mimic the fluctuations in endothelial oxygenation that occur during I/R we exposed cultured human umbilical vein EC (HUVEC) to hypoxia (1% O(2) for 4 h) followed by re-oxygenation (21% O(2) for 1 h-24 h). We observed transient expression of pro-inflammatory molecules (E-selectin, VCAM-1 and IL-8) and sustained expression of A20 in HUVEC exposed to hypoxia/re-oxygenation. The effect of A20 on endothelial responses to hypoxia/re-oxygenation was assessed. We observed that pre-treatment of HUVEC with an adenovirus containing A20 (Ad-A20) suppressed activation of NF-kappaB and induction of pro-inflammatory molecules by hypoxia/re-oxygenation, whereas a control adenovirus had little or no effect. Thus the induction of A20 may form a negative feedback loop in pro-inflammatory signalling in cells exposed to hypoxia/re-oxygenation. To validate our cell culture experiments we examined the role of A20 in renal responses to I/R. We observed that A20 was induced in rat kidneys exposed to I/R. Moreover, pre-treatment of animals with Ad-A20 significantly reduced acute tubular necrosis, renal expression of VCAM-1 and NF-kappaB activation in response to I/R, whereas pre-treatment with control adenovirus did not. Our observations suggest that A20 maintains physiological homeostasis in kidneys exposed to I/R by protecting them from inflammation and injury.
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PMID:The A20 gene protects kidneys from ischaemia/reperfusion injury by suppressing pro-inflammatory activation. 1894 30