Leukemia Inhibitory Factor Is Involved in Tubular Regeneration after Experimental Acute Renal Failure

Jun Yoshino, Toshiaki Monkawa, Mihoko Tsuji, Matsuhiko Hayashi, Takao Saruta

研究成果: Article査読

54 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3090-3101
ページ数12
ジャーナルJournal of the American Society of Nephrology
14
12
DOI
出版ステータスPublished - 2003 12月

ASJC Scopus subject areas

  • 医学一般

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