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 renal growth hormone--insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth hormone-IGF-I system may participate in the natural repair. We examined the IGF-I system in rat kidneys subjected to 60 minute ischemia compared to sham operated controls. Two days after injury, growth hormone receptor mRNA and IGF-I mRNA levels fell approximately 9 to 33% of control values. This was associated with a reduction in kidney immunoreactive IGF-I levels. In contrast, IGF-I receptor mRNA abundance was unchanged. However, plasma membrane IGF-I receptor binding on day 2 and day 7 was near double the control values (P < 0.01). Scatchard analysis revealed a near twofold increase in receptor number. Since receptor mRNA levels were unchanged, this implies receptor protein up-regulation. In contrast to unchanged IGF-I receptor mRNA levels, the abundance of mRNA levels of insulin-like growth factor binding proteins (IGFBP) -2, -3, -4 and -5 fell approximately 14 to 62% of control levels day 2 after injury (P < 0.05), suggesting reduced IGFBP production. Thus, the renal response to ischemic ATN, namely, low IGFBP mRNA levels and high IGF-I receptor number, may function to increase IGF-I bioavailability and thereby enhance the reparative actions of local and circulating IGF-I in ischemic ATN.
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PMID:Renal growth hormone--insulin-like growth factor-I system in acute renal failure. 754 60

We have examined the response of the renal insulin-like growth factor (IGF-I) axis to acute ischemic injury in the rat Key findings included a decrease in IGF-I mRNA and peptide levels, a decrease in GH receptor gene plus protein expression and a decrease in the IGF binding proteins except for IGF binding protein I. Administration of GH to compensate for the reduced GH receptor binding corrected the IGF-I mRNA levels suggesting a relative GH deficiency. Interestingly, IGF-I receptor mRNA levels were unchanged while plasma membrane IGF-I receptor number increased two fold. This appeared to be due to a redistribution of receptors to a membrane location. IGF-I receptor autophosphorylation and tyrosine kinase activity were intact despite severe uremia for up to 6 days. We propose that this increase of functional IGF-I receptors following acute tubular necrosis will sensitize the kidney to the administration of exogenous IGF-I.
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PMID:The insulin-like growth factor-I axis in acute renal failure. 957 61

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