Insulin-like growth factor-1 enhances epidermal growth factor receptor activation and renal tubular cell regeneration in postischemic acute renal failure.

J. J. Lin, A. V. Cybulsky, P. R. Goodyer, R. N. Fine, Frederick J. Kaskel

Research output: Contribution to journalArticle

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Abstract

Growth factors such as insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and hepatocyte growth factor have been shown to accelerate the recovery from postischemic acute renal failure (ARF) with a concomitant increase in DNA synthesis. Interactions between growth factors have been demonstrated in a number of in vitro studies. This study examined the effect of exogenous IGF-1 on the DNA synthesis and EGF receptor (EGF-R) activation in postischemic rat kidneys. Thirty minutes after the relief of 30-minute total occlusion of the left renal artery in anesthetized 225 to 300 gm Sprague-Dawley rats, either IGF-1 (75 micrograms/kg) or normal saline solution (NS, 0.2 ml) was given by intravenous bolus, followed by twice daily subcutaneous injections of IGF-1 (50 micrograms/kg) or 0.2 ml NS for 4 days, respectively, in IGF-1-Tx) and NS treated (NS-Tx) groups (n = 8 each). On the day after the completion of treatment, inulin clearance (ml/kg/min) of the postischemic kidneys in the IGF-1-Tx group was significantly higher (p < 0.01) than inulin clearance of kidneys in the NS-Tx group. This was associated with improved kidney morphology. IGF-1 treatment also enhanced the labeling index of 5-bromo-2'-deoxyuridine (percent of stained tubule cells), a marker for active DNA synthesis, in the outer medulla of postischemic kidneys at 1 day and 2 days after the injury. EGF-R tyrosine phosphorylation (which reflects receptor activation) increased in postischemic kidneys in both NS-Tx (n = 5) and IGF-1-Tx (n = 3) groups 1 day after the injury as compared with nonischemic contralateral kidneys. In the IGF-1-Tx group there was also increased iodine 125-labeled EGF binding and EGF-R protein. Our results demonstrate a beneficial effect of IGF-1 on postischemic ARF. Furthermore, they suggest that EGF-R activation is involved in tubular regeneration and that IGF-1 may enhance EGF-R activation by increasing EGF-R expression.

Original languageEnglish (US)
Pages (from-to)724-733
Number of pages10
JournalJournal of Laboratory and Clinical Medicine
Volume125
Issue number6
StatePublished - Jun 1995
Externally publishedYes

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Somatomedins
Epidermal Growth Factor Receptor
Acute Kidney Injury
Regeneration
Chemical activation
Epidermal Growth Factor
Kidney
Inulin
DNA
Intercellular Signaling Peptides and Proteins
Kidney Medulla
Phosphorylation
Hepatocyte Growth Factor
Wounds and Injuries
Renal Artery
Bromodeoxyuridine
Subcutaneous Injections
Genetic Markers
Sodium Chloride
Iodine

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Insulin-like growth factor-1 enhances epidermal growth factor receptor activation and renal tubular cell regeneration in postischemic acute renal failure. / Lin, J. J.; Cybulsky, A. V.; Goodyer, P. R.; Fine, R. N.; Kaskel, Frederick J.

In: Journal of Laboratory and Clinical Medicine, Vol. 125, No. 6, 06.1995, p. 724-733.

Research output: Contribution to journalArticle

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