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)

Adenine nucleotides speed structural and functional recovery when administered after experimental renal injury in the rat and stimulate proliferation of kidney epithelial cells. As cell migration is a component of renal regeneration after acute tubular necrosis, we have used an in vitro model of wound healing to study this process. High density, quiescent monkey kidney epithelial cultures were wounded by mechanically scraping away defined regions of the monolayer to simulate the effect of cell loss after tubular necrosis and the number of cells that migrated into the denuded area was counted. Migration was independent of cell proliferation. Provision of adenosine, adenine nucleotides, or cyclic AMP increased the number of migrating cells and accelerated repair of the wound. Other purine and pyrimidine nucleotides were not effective. Arginine-glycine-aspartic acid-serine peptide, which blocks the binding of extracellular fibronectin to its cell surface receptor, completely inhibited migration in the presence or absence of ADP. Very low concentrations of epidermal growth factor (K0.5 approximately 0.3 ng/ml) stimulated migration, whereas transforming growth factor-beta 2 was inhibitory (Ki approximately 0.2 ng/ml). Thus, adenosine and/or adenine nucleotides released from injured or dying renal cells, or administered exogenously, may stimulate surviving cells in the wounded nephron to migrate along the basement membrane, thereby rapidly restoring tubular structure and function.
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PMID:Adenine nucleotides stimulate migration in wounded cultures of kidney epithelial cells. 163 17

Tubular cells can either unergo hyperplasia or hypertrophy, two totally different growth responses. Hyperplasia with mitogenesis of tubular cells plays a central role in the regeneration of functional tubular epithelium subsequent to acute tubular necrosis. Several growth factors acting in concert are involved in this proliferative response of tubular cells. The molecular mechanisms how mitogenic signals are transduced to the nucleus are relatively well characterized. Complex oscillation patterns of cell cycle-associated proteins like cyclins and various kinases are pivotal for the progression of quiescent tubular cells through mitosis. In contrast to the mitogenic growth response of regenerating tubular cells, cellular hypertrophy is less well understood. Hypertrophic cells are arrested in the G1-phase of the cell cycle and increase their size, protein and RNA content, but do normally not replicate their DNA. Such an enlargement of tubular cells often occurs in more chronic situations of renal damage in which remnant nephrons adapt their function to the increasing need. However, evidence exists that hypertrophic tubules are finally joined into the process of maladaptation of renal function leading to tubular atrophy, interstitial scarring, and progression of renal disease. It appears that transforming growth factor-beta is involved in the hypertrophy of tubular cells. The present review will address more recent progress in understanding the mechanism of tubular growth at a cellular level. A better knowledge of the molecular factors may ultimately lead to therapeutic strategies preventing the progression of renal and speeding up renal recovery after acute renal failure.
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PMID:Cellular mechanisms of tubule hypertrophy and hyperplasia in renal injury. 756 79

Cyclosporine A (CsA) is a potent immunosuppressive drug that inhibits the transcription of several proinflammatory cytokines including interleukin-2. In contrast, CsA stimulates transcription of the pleuripotent cytokine, transforming growth factor-beta (TGF beta). Since the effect of CsA in transplant recipients is unpredictable, we examined whether tissue levels of TGF beta protein in renal allografts correlate with in vivo CsA responsiveness. Intra-allograft TGF beta protein content was assessed in renal biopsies by immunohistochemical means using the mouse anti-TGF beta monoclonal antibody (Mab), 1D11. We studied 68 specimens: 21 with acute CsA toxicity (ACT), 11 with acute tubular necrosis (ATN) and 36 with acute cellular rejection (ACR). Intensity of TGF beta immunostaining was evaluated in a blinded fashion using a scale from 0 to 3+. In biopsies with histological evidence of CsA toxicity, 77% demonstrated intense (2 to 3+) TGF beta immunostaining. TGF beta protein was detected in both proximal and distal tubules but was either absent or present in low levels within glomeruli and interstitium. In contrast, only one of the 11 biopsies with ATN had minimal staining (1+) for TGF beta. The remaining 10 biopsies with ATN were negative for TGF beta immunostaining. In biopsies with ACR, the levels of renal TGF beta were more variable with 36% showing intense (2 to 3+) staining and 64% having minimal or no (0 to 1+) tubular TGF beta. Within the first 18 months post-transplantation, patients with intense TGF beta staining and ACR underwent an average of 4.1 +/- 1.8 allograft biopsies and suffered 33% graft losses. During the same period of time, the patients with ACR and absent or low (0 to 1+) TGF beta levels underwent only 2.1 +/- 1.2 biopsies, maintained better late renal function and suffered 4% graft losses. In conclusion, we demonstrate that TGF beta protein levels in renal allografts correlate with CsA effect and differentiate ACT from ATN. In CsA treated patients who develop ACR, TGF beta levels predict the subsequent clinical course and graft function. Therefore, evaluating tissue levels of TGF beta may offer unique diagnostic and prognostic benefits in the care of patients receiving CsA based immunosuppression.
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PMID:Increased renal tubular expression of transforming growth factor beta in human allografts correlates with cyclosporine toxicity. 891 30

HIV-associated nephropathy is manifested by heavy proteinuria and renal insufficiency and characterized pathologically by the collapsing variant of focal and segmental glomerulosclerosis with acute tubular necrosis and mild interstitial inflammation. Untreated, it may result in end-stage renal disease in as little as 4 months. It may present in patients with any manifestation of HIV infection, and affects predominantly black individuals. Insights into pathogenesis have come from a transgenic mouse model, renal cell cultures, and from study of human biopsy material. Although the pathogenesis is not completely understood, current considerations revolve around the role of HIV or protein in renal epithelium and the effects of cytokines, including transforming growth factor-beta and basic fibroblast growth factor, on renal structures. Therapy with zidovudine, corticosteroids, or angiotensin-converting enzyme inhibitors has met with modest success; to date, protease inhibitors have not been assessed.
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PMID:Distinguished Scientists Lecture Series. HIV-associated nephropathy. 1051 88

Human immunodeficiency virus-associated nephropathy (HIVAN) is a clinicopathological entity characterised by proteinuria, rapidly developing azotemia and histologically by collapsig variant of focal and segmental glomerulosclerosis with acute tubular necrosis and mild interstitial inflammation. Untreated, it may result in end stage renal disease (ESRD) in as little as four months. The incidence of HIVAN continues to increase and is the single most common cause of chronic renal disease in HIV-1 seropositive patients. It affects predominantly black individuals. Exact pathogenesis is still not clear but a great deal of progress has been made in the recent past by studies on transgenic mouse model, renal cell cultures and from study of human biopsy material. Current considerations revolve around the role of HIV or protein in renal epithelium and the effects of cytokines, including transforming growth factor-beta and basic fibroblast growth factor on renal structures. Different modalities of treatment with corticosteroids, zidovudine or angiotensin converting enzyme inhibitors have been tried with modest success.
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PMID:Human immunodeficiency virus-associated nephropathy. 1183 70

Subcutaneous injection of sodium arsenite (NaAs, 12.5 mg/kg) into BALB/c [wild-type (WT)] mice causes acute renal dysfunction characterized by severe hemorrhages, acute tubular necrosis, and cast formation, with increases in serum blood urea nitrogen and creatinine levels. Concomitant enhancement in intrarenal interferon (IFN)-gamma expression prompted us to examine its roles in this pathology. IFN-gamma-deficient (IFN-gamma-/-) mice exhibited higher serum blood urea nitrogen and creatinine levels and exaggerated histopathological changes, compared with WT mice. Eventually, IFN-gamma-/- mice exhibited a high mortality (87.5%) within 24 hours after NaAs challenge, whereas most WT mice survived. The intrarenal arsenic concentration was significantly higher in IFN-gamma-/- mice later than 10 hours after NaAs treatment, with attenuated intrarenal expression of multidrug resistance-associated protein (MRP) 1, a main transporter for NaAs efflux, compared with WT mice. NF-E2-related factor (Nrf) 2 protein, a transcription factor crucial for MRP1 gene expression, was similarly increased in the kidneys of both strains of mice after NaAs treatment. In contrast, the absence of IFN-gamma augmented transforming growth factor-beta-Smad3 signal pathway and eventually enhanced the expression of activating transcription factor 3, which is presumed to repress Nrf2-mediated MRP1 gene expression. Thus, IFN-gamma can protect against NaAs-induced acute renal injury, probably by maintaining Nrf2-mediated intrarenal MRP1 gene expression.
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PMID:Interferon-gamma plays protective roles in sodium arsenite-induced renal injury by up-regulating intrarenal multidrug resistance-associated protein 1 expression. 1700 72