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PMID:14638908

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Citation

Yoshino, J, Monkawa, T, Tsuji, M, Hayashi, M and Saruta, T (2003) Leukemia inhibitory factor is involved in tubular regeneration after experimental acute renal failure. J. Am. Soc. Nephrol. 14:3090-101

Abstract

Leukemia inhibitory factor (LIF) is known to play a crucial role in the conversion of mesenchyme into epithelium during nephrogenesis. This study was carried out to test the hypothesis that LIF and LIF receptor (LIFR) are involved in the renal epithelial regeneration after acute renal failure. First, the authors investigated the spatiotemporal expression of LIF and LIFR in fetal and adult rat kidney. In developing kidney, LIF was expressed in the ureteric buds and LIFR was located in nephrogenic mesenchyme and the ureteric buds; in adult kidney, LIF and LIFR expression was confined to the collecting ducts. Next, the authors examined the expression of LIF and LIFR during the recovery phase after ischemia-reperfusion injury. Real-time PCR analysis revealed that LIF mRNA expression was significantly increased from day 1 to day 7 after reperfusion and that LIFR mRNA was upregulated from day 4 to day 14. Histologic analysis demonstrated that the increased expression of LIF mRNA and protein was most marked in the outer medulla, especially in the S3 segment of the proximal tubules. To elucidate the mitogenic role of LIF in the regeneration process, cultured rat renal epithelial (NRK 52E) cells were subjected to ATP depletion (an in vitro model of acute renal failure), and LIF expression was found to be enhanced during recovery after ATP depletion. Blockade of endogenous LIF with a neutralizing antibody significantly reduced the cell number and DNA synthesis during the recovery period. These results suggest that LIF participates in the regeneration process after tubular injury.

Links

PubMed

Keywords

Acute Kidney Injury; Adenosine Triphosphate/physiology; Age Factors; Animals; Interleukin-6/analysis; Interleukin-6/biosynthesis; Interleukin-6/genetics; Interleukin-6/physiology; Kidney/blood supply; Kidney/chemistry; Kidney Tubules/physiology; Leukemia Inhibitory Factor; Leukemia Inhibitory Factor Receptor alpha Subunit; RNA, Messenger/biosynthesis; Rats; Rats, Sprague-Dawley; Receptors, Cytokine/analysis; Receptors, Cytokine/biosynthesis; Receptors, OSM-LIF; Regeneration; Reperfusion Injury/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:LIFR

enables

GO:0019955: cytokine binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:LIFR

involved_in

GO:0031100: animal organ regeneration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:LIFR

enables

GO:0004923: leukemia inhibitory factor receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:LIF

enables

GO:0005146: leukemia inhibitory factor receptor binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:LIF

involved_in

GO:0031100: animal organ regeneration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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