Dysregulated heme oxygenase-ferritin system in pterygium pathogenesis.
Dysregulated heme oxygenase-ferritin system in pterygium pathogenesis.
复制标题
DOI：
10.1097/ico.0b013e3182936915
复制
发表时间：
2013-09
期刊：
影响因子：
2.8
通讯作者：
Bellner L
中科院分区：
文献类型：
--
作者：
Fox T;Gotlinger KH;Dunn MW;Lee OL;Milman T;Zaidman G;Schwartzman ML;Bellner L
环氧合酶 (COX)、脂氧合酶 (LOX) 和细胞色素 P450 单加氧酶 (CYP) 衍生的类花生酸与眼表炎症和新生血管形成有关。这些类二十烷酸受到血红素加氧酶 (HO) 和铁蛋白等酶的调节。对接受手术翼状胬肉切除术的患者的翼状胬肉进行定量 PCR 和基于 LC-MS/MS 的脂质组学研究。对照组织由供体角膜组成。此外，还对手术前收集的患者泪液进行了基于 LC-MS/MS 的脂质组学分析。与对照组织相比，翼状胬肉中 HO-2（组成型 HO 亚型）的 mRNA 表达上调 40%，而诱导型 HO-1 的 mRNA 水平下调超过 50%。与对照相比，翼状胬肉的 CYP4B1 mRNA 水平增加了大约 2 倍。组织脂质组学分析表明，与对照相比，翼状胬肉中 PGE2 和 TxB2 水平加倍。在 LOX 衍生的代谢物中，与对照（586.2±213.5 pg/mg 蛋白）相比，翼状胬肉中的抗炎 15-HETE 水平显着降低（79.3±48.11 pg/mg 蛋白），而促炎性 LOX 和 CYP4B1 衍生的 12-HETE 水平在翼状胬肉中高出 10 倍（2768±832.3 pg/mg 蛋白质）与对照（231.4±87.35 pg/mg 蛋白质）相比。 PGE2 和 HETE 也存在于翼状胬肉患者的眼泪中，但在健康志愿者的眼泪中未检测到。与对照相比，翼状胬肉中铁蛋白轻链和重链 mRNA 表达水平分别降低 60% 和 30%。我们认为，功能失调的 HO-铁蛋白系统会导致促炎介质水平升高，从而导致翼状胬肉的炎症特征。
Cyclooxygenases (COX), lipoxygenases (LOX) and cytochrome P450 monooxygenases (CYP) derived eicosanoids have been implicated in ocular surface inflammation and neovascularization. These eicosanoids are subjected to regulation by enzymes such as heme oxygenases (HO) and ferritin. Quantitative PCR and LC-MS/MS based lipidomics were performed on pterygia from patients undergoing surgical pterygium excision. Control tissues consisted of donor corneas. In addition, LC-MS/MS-based lipidomics was performed on tears collected from patients prior to surgery. mRNA-expression of HO-2, the constitutive HO isoform, was upregulated by 40 % in pterygia as compared to control tissue, while the mRNA level of the inducible form, HO-1, was downregulated by more than 50 %. Levels of CYP4B1 mRNA showed an approximate 2-fold increase in pterygia compared to control. Lipidomics analysis of tissues indicated a doubling in PGE2 and TxB2 levels in pterygia as compared to control. Among LOX-derived metabolites, the anti-inflammatory 15-HETE levels were significantly reduced in pterygia (79.3±48.11 pg/mg protein) as compared to control (586.2±213.5 pg/mg protein), whereas pro-inflammatory LOX- and CYP4B1-derived 12-HETE levels were 10-fold higher in pterygia (2768±832.3 pg/mg protein) compared to control (231.4±87.35 pg/mg protein). PGE2 and the HETEs were also present in tears from patients with a pterygium, but were not detected in tears from healthy volunteers. Ferritin light and heavy chain mRNA expression levels were 60 % and 30 % lower in pterygia as compared to control. We believe a dysfunctional HO-Ferritin system leads to increased levels of proinflammatory mediators, thus contributing to the inflammation characteristic of pterygia.