mPGES-1-Derived PGE(2) Contributes to Indoxyl Sulfate-Induced Mesangial Cell Proliferation
mPGES-1-Derived PGE(2) Contributes to Indoxyl Sulfate-Induced Mesangial Cell Proliferation
复制标题
mPGES-1 衍生的 PGE(2) 有助于硫酸吲哚酚诱导的系膜细胞增殖
DOI：
10.1159/000480369
复制
发表时间：
2017
影响因子：
--
通讯作者：
Jia Zhanjun
中科院分区：
文献类型：
--
作者：
Li Shuzhen;Sun Zhenzhen;Ding Guixia;Gong Wei;Yu Jing;Xia Weiwei;Huang Songming;Zhang Aihua;Zhang Yue;Jia Zhanjun
背景与目的我们曾报道硫酸吲哚酚（indoxyl sulfate，IS）可通过环氧化酶（cyclooxygenase，考克斯）-2依赖性机制引起系膜细胞（mesangial cell，MC）增殖。然而，具体的前列腺素有助于考克斯-2对IS诱导的MC增殖的影响仍然未知。本研究旨在探讨微粒体前列腺素E合成酶-1（mPGES-1）衍生的前列腺素E2（PGE 2）在IS诱导MC增殖中的作用。在另一个实验设置中，PGE 2被施加到MC检查其对MC增殖的直接影响，以及前列腺素E受体（EPs）的调节通过qRT-PCR.ResultsWith管理的IS，mPGES-1（而不是mPGES-2和胞质PGES）在蛋白质和mRNA水平显着上调与促进MC增殖。有趣的是，沉默mPGES-1减少了S和G2期的细胞数量，并阻断了细胞周期蛋白A2和细胞周期蛋白D1的上调，同时抑制了IS处理后PGE 2的释放，表明mPGES-1衍生的PGE 2可能有助于MC增殖。此外，我们证实外源性PGE 2可直接触发MCs的增殖反应.最后，我们观察到经PGE 2处理的系膜细胞中EP 2的选择性上调和经IS处理的系膜细胞中NF-κB的磷酸化增强，提示EP 2和NF-κB参与了这一病理过程。
Background/AimsWe previously reported that indoxyl sulfate (IS) could cause mesangial cell (MC) proliferation via a cyclooxygenase (COX)-2-dependent mechanism. However, the specific prostaglandin contributing to COX-2 effect on IS-induced MC proliferation remained unknown. Thus, the present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived Prostaglandin E2 (PGE 2) in IS-induced MC proliferation.MethodsIS was administered to the MCs with or without mPGES-1 siRNA pretreatment to induce the MC proliferation which was determined by cell cycle analysis, DNA synthesis, and the expressions of cyclins. In another experimental setting, PGE 2 was applied to the MCs to examine its direct effect on MC proliferation, as well as the regulation of prostaglandin E receptors (EPs) by qRT-PCR.ResultsWith the administration of IS, mPGES-1 (not mPGES-2 and cytosolic PGES) was significantly upregulated at both protein and mRNA levels in line with a promoted MC proliferation. Interestingly, silencing mPGES-1 reduced cell number in S and G2 phases and blocked the upregulation of cyclin A2 and cyclin D1 in parallel with blunted PGE 2 release after IS treatment, indicating that mPGES-1-derived PGE 2 could contribute to MC proliferation. Furthermore, we confirmed that exogenous PGE 2 could directly trigger the proliferative response in MCs. Lastly, we observed a selective upregulation of EP2 after PGE2 treatment and enhanced phosphorylation of NF-κB following IS administration in MCs, suggesting the potential involvements of EP2 and NF-κB in this pathological process.ConclusionmPGES-1-derived PGE 2 contributed to IS-induced mesangial cell proliferation.