IL-1β functionally attenuates ABCG2 and PDZK1 expression in HK-2 cells partially through NF-ĸB activation
IL-1β functionally attenuates ABCG2 and PDZK1 expression in HK-2 cells partially through NF-ĸB activation
复制标题
IL-1 beta 部分通过 NF-äB 激活功能性减弱 HK-2 细胞中的 ABCG2 和 PDZK1 表达
DOI：
10.1002/cbin.11100
复制
发表时间：
2019-03-01
影响因子：
3.9
通讯作者：
Wu, Huaxiang
中科院分区：
文献类型：
--
作者：
Lu, Xiaoyong;Chen, Mo;Wu, Huaxiang
长期未经治疗的高尿酸血症可能会导致痛风。最近的几项研究表明，在急性痛风发作期间，血清尿酸显著降低，这是一种以IL-1β为重点的无菌性炎症过程。然而，IL-1β本身如何改变肾小管上皮细胞尿酸转运体的表达和功能活性仍不清楚。在此，我们通过实时定量聚合酶链式反应和Western-blotting检测发现，IL-1β可以降低HK-2细胞尿酸盐外排泵ABCG2的mRNA和蛋白水平。此外，使用ABCG2特异性抑制剂和一种新的敏感和特异的检测系统，发现IL-1β也降低了ABCG2转运蛋白的活性。与NF-ĸB通路的特异性抑制剂共同孵育可部分抑制IL-1β对ABCG2的抑制作用，提示IL-1β部分通过NF-KappaB途径抑制ABCG2的表达。此外，依赖于核因子-kappaB途径的IL-1β诱导的PDZK1表达下降可能是ABCG2功能与表达失衡的原因。这些发现证明了IL-1β的一个新的作用，即它导致肾小管上皮细胞ABCG2的抑制；这个新的作用可能不包括它参与炎症介导的肾脏尿酸盐排泄过程。因此，肾小管上皮细胞尿酸重吸收的其他调节机制值得进一步研究。
Long-standing untreated hyperuricemia could lead to gout. Several recent studies have demonstrated a significant decrease of serum urate during acute gout attack, which is an aseptic inflammation process focusing on IL-1 beta. However, how IL-1 beta, by itself, alters the expression and the functional activity of urate transporters in renal tubular epithelial cells is still unclear. Herein, we revealed that IL-1 beta could attenuate the mRNA and protein levels of ABCG2, a major urate efflux pump, in HK-2 cells by real-time PCR and Western-blot assays. Moreover, using an ABCG2 specific inhibitor and a new sensitive and specific detection system, it was found that IL-1 beta also reduced the ABCG2 transporter activities. Incubation with specific inhibitors of the NF-kappa B pathway partly dampened the inhibitory effect of IL-1 beta on ABCG2, indicating that IL-1 beta reduced the ABCG2 expression partially through the NF-ĸB pathway. Furthermore, the decreased expression of PDZK1 induced by IL-1 beta, which is dependent on the NF-kappa B pathway, could account for the imbalance between the functions and expressions of ABCG2 on this status. These findings demonstrated a new role for IL-1 beta, whereby it leads to the inhibition of ABCG2 in renal tubular epithelial cells; this new role probably does not encompass its involvement in the process of renal urate excretion mediated by inflammation. Therefore, other regulation mechanisms of urate reabsorption in renal tubular epithelial cells deserve to be examined in further studies.