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 roles of growth factors in the pathogenesis of various forms of acute and chronic renal disease are largely putative. Nevertheless, there is a growing body of information that links specific growth factors to particular forms of renal injury. In all instances, it is supposed that such associations are not necessarily unique and that multiple cytokines probably interact to determine the pattern of injury or the regenerative response to such injury. Regeneration of tubular epithelium after acute tubular necrosis involves upregulation of the epidermal growth factor (EGF) receptor. Early studies of exogenously administered EGF indicate that the severity and duration of renal failure may be attenuated by this growth factor. Thus far, the observed responses have been limited and the role of EGF as a therapeutic agent requires more study. The mechanism of generation of tubulointerstitial injury in most forms of renal disease is difficult to understand. Early in vitro studies of growth factor production by tubular cells (in the absence of any infiltrating cells) indicate that platelet-derived growth factor produced by the medullary collecting duct is mitogenic for renal medullary fibroblasts, suggesting a paracrine growth system in this region of the kidney. Insulin-like growth factor I has also been shown to be produced by collecting duct cells. Its production is increased by EGF, and its association with certain forms of renal hypertrophy, i.e., diabetes and hypersomatotrophic states, implies its participation in the hypertrophic growth response. Platelet-derived growth factor is a potent mitogen for glomerular mesangial cells, and its production is regulated by a variety of cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evolving role of growth factors in the renal response to acute and chronic disease. 159 57

It is known that a series of mediators, so-called growth factors, are able to induce hypertrophy of the kidney in a patient after uninephrectomy. The first investigator who demonstrated this phenomenon was C. Sacerdotti, an Italian pathologist of Bizzozero's School in Turin, who published an important report in 1896. He attempted to explain how compensatory renal hypertrophy occurred and how this hypertrophy might be induced in a normal dog. Interestingly, he demonstrated that when the kidneys of a normal dog received a blood transfusion from uni- or binephrectomized dogs several mitoses appeared in the renal epithelium. These mitoses, expression of renal hypertrophy, were more evident in dogs receiving several blood transfusions for 6-7 days. He concluded that hypertrophy was induced by specific substances circulating in the blood of uni- or binephrectomized dogs. This hypothesis was in the next 100 years confirmed by the discovery of renal growth factors such as epidermal growth factor, insulin-like growth factor-1, hepatocyte growth factor, platelet-derived growth factor and others. The pathogenic role of these mediators is evident in the recovery of tubules after acute tubular necrosis and in the remnant glomeruli after glomerular damage. Today, attempts to use these growth factors for improving renal function in patients with acute tubular necrosis and to block their action in the progression of renal damage in chronic glomerulonephritides are under investigation. Future trends in these growth factors will be set by drug companies designing specific therapies such as gene therapy. In conclusion, the outstanding observation by Sacerdotti, over a century ago, remains an important step in nephrologic history for prognosis and therapy of renal diseases.
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PMID:Renal growth factors: past, present and future. 1021 33

The aim of our study was to correlate intragraft mRNA expression of cytokines and growth factors with histopathologic features in renal allograft biopsies. Fifty-six core biopsies performed in 51 kidney transplant recipients were assessed by the Banff '97 classification. Tubular and glomerular expressions of IFN-gamma, TGF-beta1, and PDGF-B as well as IL-2, IL-6, and IL-10 mRNA were assessed using semiquantitative RT-PCR in situ. No significant differences were noted between acute cellular and vascular rejection with regard to the glomerular and tubular mRNA expression of cytokines examined. We observed a positive correlation between tubular and glomerular IL-10 and IFN-gamma mRNAs during acute rejection. In chronic rejection the mRNA expression levels of IFN-gamma and IL-2, IL-6, and IL-10 did not differ from those of acute rejection; moreover, the glomerular expression of mRNA for TGF-beta1 (P < .05) and PDGF-B (P < .1) was even lower than during acute rejection episodes. Both tubular and glomerular IL-2, TGF-beta1, and PDGF-B mRNA expression levels in biopsies with acute rejection were significantly higher than in acute tubular necrosis (ATN). Biopsy samples with borderline changes exhibited the lowest levels of cytokine gene expression and were close to the intensity of control specimens obtained from living donor kidney biopsies taken during organ harvest. Our data failed to show a dichotomy between Th1 and Th2 cytokine activation in biopsy specimens from kidney allograft recipients; both Th1- and Th2-derived cytokines were involved to similar extents in rejection processes.
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PMID:Intragraft mRNA expression of cytokines and growth factors in human kidney allograft biopsies by in situ RT-PCR analysis. 1584 25