Insulin-like growth factor-1 (IGF-1) enhances recovery from HgCl2-induced acute renal failure: the effects on renal IGF-1, IGF-1 receptor, and IGF-binding protein-1 mRNA.
Several growth factors have been found to play an important role in the recovery from acute renal failure (ARF). The effect of the continuous subcutaneous infusion of human recombinant insulin-like growth factor (IGF)-1 (125 micrograms daily by osmotic minipumps) in a rat model of mercuric chloride (HgCl2)-induced ARF was examined. HgCl2 (4 mg/kg) induced ARF with a mortality that was unaffected by IGF-1. However, IGF-1 significantly enhanced functional and histologic recovery in the survivors, as measured by serum creatinine and creatinine clearance and by histologic scoring. Solution hybridization RNAase protection assays showed that renal IGF-1 mRNA, IGF-1 receptor (IGF-1R) mRNA, and IGF-binding protein-1 (IGFBP-1) mRNA were unaffected by exogenous IGF-1, but this treatment significantly increased renal IGF-1 in ARF rats compared with normal rats and ARF rats not receiving IGF-1. After ARF renal mRNA for IGF-1 was decreased, IGF-1R was unchanged and IGFBP-1 was increased. Similar changes occurred in IGF-1-infused ARF rats. Thus, (1) IGF-1 enhances recovery from nephrotoxic ARF both functionally and histologically; (2) in nephrotoxic ARF, there is (a) a reduction in IGF-1 mRNA expression that is not prevented by IGF-1 infusion, and (b) an increase in renal IGFBP-1 mRNA. This may allow a significant increase in renal IGF-1 levels in IGF-1-infused ARF rats, despite the decrease in renal IGF-1 mRNA. A local increase in renal IGFBP-1 and IGF-1 may explain the accelerated recovery from ATN in this model. It was concluded that HgCl2-induced ARF is amenable to improvement by IGF-1 infusion and that the increase in renal IGFBP-1 mRNA may be an important modulator in the recovery of the kidney.
Friedlaender
M
M
Nephrology Service, Hadassah University Hospital, Jerusalem, Israel.
Popovtzer
M M
MM
Weiss
O
O
Nefesh
I
I
Kopolovic
J
J
Raz
I
I
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008627:Mercuric Chloride; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017526:Receptor, IGF Type 1 / Q000235:genetics
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D008627:Mercuric Chloride; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1