Korean J Nephrol.
1998 May;17(3):366-375.
Alteration of Insulin-like Growth Factor (IGF)-I and IGF-binding Proteins in Rat with Acute Renal Failure
- Affiliations
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- 1Department of Pediatrics, Chonbuk National University Medical School, Chonju, Chonbuk, Korea.
- 2Department of Internal Medicine, Chonbuk National University Medical School, Chonju, Chonbuk, Korea.
- 3Institute for Medical Science, Chonbuk National University Medical School, Chonju, Chonbuk, Korea.
Abstract
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Acute renal failure(ARF) usually has more than one cause and almost always includes an ischemic or nephrotoxic component to varying degrees. Regeneration and repair appear to be modulated by circulating and locally produced growth factors including insulin-like growth factors(IGFs). This study examined the change of serum and renal IGF-IGFBP axis in uremic rat by using IGF-I radioimmunoassay, Western ligand blot, immunohistochemical study and Northern blot analysis. Sera and kidney samples were obtained before and after 1, 3, 5, 7, 10 and 14 days of 45 minutes bilateral renal pedicle clamping. The results were as follows.
1) Following bilateral renal pedicle clamping, rats lost their weight, reaching a maximum after 3 days of ischemic injury. On day 10 uremic rats were still below their starting weights.
2) Following acute ischemic renal injury, serum creatinine rose, reaching a maximum after 3 days. By the 10th day serum creatinine levels had fallen to normal values.
3) Serum IGF-I concentration after 1 day following ischemic injury was significantly decreased compared to preischemic value. However the decreased level was returned to normal value after 3 days of ischemic injury.
4) The alteration of serum IGFBP profiles was observed in uremic rat. The 37-45 kDa sized IGFBP (probably IGFBP-3) was increased after 3 days of ischemic renal injury and continued until 10 days of ischemic injury. Another 28 kDa sized IGFBP also increased after 3 days of ischemic injury.
5) In preischemic kidney, immunoreactive IGF-I were primarily present in cortical tubule. However, IGF-I was markedly decreased on day 3 uremic rat.
6) IGFBP-3 and -7 mRNA in uremic kidney were temporally decreased on day 1 but increased to normal or higher levels after 3 days of ischemic renal injury. IGFBP-1 and -4 mRNA were markedly increased after 1 day and maintained high levels until 5 days(IGFBP-1) and 14 days(IGFBP-4) of ischemic renal injury.
These findings suggest that IGF-IGFBP axis may involve in the pathogenesis or the recovery from acute renal failure.