Leukemia inhibitory factor is involved in tubular regeneration after experimental acute renal failure
Leukemia inhibitory factor is involved in tubular regeneration after experimental acute renal failure
复制标题
DOI：
10.1097/01.asn.0000101180.96787.02
复制
发表时间：
2003-12-01
影响因子：
13.6
通讯作者：
Saruta, T
中科院分区：
文献类型：
--
作者：
Yoshino, J;Monkawa, T;Saruta, T
白血病抑制因子（LIF）在肾形成过程中间质向上皮的转化中起着至关重要的作用。本研究旨在验证急性肾功能衰竭后LIF和LIF受体（LIFR）参与肾上皮再生的假设。首先，作者研究了胎儿和成年大鼠肾脏中LIF和LIFR的时空表达。在发育肾中，LIF在输尿管芽中表达，LIFR位于肾原间质和输尿管芽中；在成人肾脏中，LIF和LIFR的表达仅限于集合管。接下来，作者检测了缺血再灌注损伤后恢复期LIF和LIFR的表达。Real-time PCR分析显示，再灌注后第1天至第7天LIF mRNA表达显著升高，第4天至第14天LIFR mRNA表达上调。组织学分析表明，LIF mRNA和蛋白的表达增加在外髓质最为明显，尤其是在近端小管S3段。为了阐明LIF在再生过程中的有丝分裂作用，我们将培养的大鼠肾上皮细胞（NRK 52E）进行ATP耗尽（急性肾功能衰竭的体外模型），发现在ATP耗尽后的恢复过程中LIF表达增强。用中和抗体阻断内源性LIF可显著减少恢复期的细胞数量和DNA合成。这些结果表明，LIF参与了小管损伤后的再生过程。
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 I 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.