Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.
Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.
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DOI：
10.1038/srep32119
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发表时间：
2016-08-26
影响因子：
4.6
通讯作者：
Yatomi Y
中科院分区：
文献类型：
--
作者：
Sato M;Ikeda H;Uranbileg B;Kurano M;Saigusa D;Aoki J;Maki H;Kudo H;Hasegawa K;Kokudo N;Yatomi Y
1-磷酸鞘氨醇（S1 P）在人类肝纤维化或炎症中的作用尚未完全研究。S1 P1和S1 P3与S1 P2中的哪一种受体可能参与其发病机制仍存在争议。为了阐明这些问题，入组了80例因肝细胞癌接受肝切除术的患者和9例因转移性肝肿瘤接受肝切除术的患者。在背景、非肿瘤肝组织中分析S1 P代谢。与0-2期和正常肝脏相比，3-4期肝纤维化患者的鞘氨醇激酶1（SK 1）mRNA水平升高，但SK 2 mRNA水平未升高。然而，S1 P并没有增加，在先进的纤维化肝脏，其中S1 P转运蛋白自旋同源物2（SPNS 2），但不是S1 P降解酶的mRNA水平增强。此外，在晚期肝纤维化中，S1 P2的mRNA水平升高，而S1 P1或S1 P3的mRNA水平未升高。纤维化肝脏中SK 1、SPNS 2和S1 P2 mRNA水平的增加与肝脏中α-平滑肌肌动蛋白mRNA水平以及血清ALT水平相关。总之，S1 P可能在人肝脏中主动产生、转运到细胞外并与其特异性受体结合，从而在纤维化或炎症中发挥作用。肝纤维化中S1 P代谢的改变可能是其治疗靶点。
The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3–4 compared to those with 0–2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.