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 previously reported that following bilateral acute tubular necrosis (ATN) profound changes in the intrarenal insulin-like growth factor-I axis occurs which are unrelated to altered nutritional intake. In this current report we studied rats with unilateral ATN to assess whether these changes reflect a response to acute injury or the accompanying uremia. Compared to the contralateral kidney, the injured kidney showed an increase in IGF-I receptor number without a change in IGF-I receptor mRNA levels, a decrease in IGF-I mRNA and IGF-I protein levels, a decrease in growth hormone (GH) receptor mRNA abundance and receptor binding. There was also a decrease in IGF binding protein-2, -3 and -5 mRNA levels together with a fall in protein products. Since this unilateral ATN model excludes the influence of uremia and reduced nutritional intake, we surmised that these changes reflect a direct response to injury. Next, because of the reduced GH receptor binding noted above and the reported decrease in epidermal growth factor (EGF) expression in ATN, we tested the thesis that the low kidney IGF-I mRNA levels in ATN are partly due to a relative or absolute deficiency of these hormones. Administration of EGF or GH promptly increased ATN kidney IGF-I mRNA levels to control kidney values, lending support to the thesis. The response to EGF also suggests that the salutary effect of EGF treatment in ATN may partly be mediated by stimulating IGF-I production.
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PMID:Response of the intrarenal insulin-like growth factor-I axis to acute ischemic injury and treatment with growth hormone and epidermal growth factor. 882 16

Following acute tubular necrosis (ATN), kidney plasma membrane insulin-like growth factor-I (IGF-I) receptor number increases markedly, although IGF-I receptor mRNA levels do not change. To determine whether this increase could represent a redistribution of intracellular receptors and whether receptor function is intact in acute uremia, rats with ATN of 2 days duration and pair-fed controls were studied. Skeletal muscle receptor binding was unchanged. In contrast, binding to receptors in solubilized cortex and isolated cortical plasma membranes increased significantly due to an increase in receptor number. However, the increase in membrane binding was threefold greater than the increase in solubilized cortex binding. This indicates that the increase in total cellular IGF-I receptors can only account for a minor portion of the increase in abundance of plasma membrane receptors number and is consistent with a redistribution of receptors from an intracellular to a membrane location as the major mechanism. Autophosphorylation and receptor kinase activity were unaffected by the uremia (blood urea nitrogen of approximately 198 mg/dl). Since these early steps of IGF-I receptor signaling are intact early in acute uremia, it is likely that at this time in the course of the disease the increase in receptor number will heighten the sensitivity to IGF-I and may thus favor its participation in renal repair.
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PMID:IGF-I receptor binding, autophosphorylation, and kinase activity in kidney and muscle of acutely uremic rats. 908 75

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