Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway.
Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway.
复制标题
DOI：
10.1186/1475-2840-12-37
复制
发表时间：
2013-02-26
影响因子：
9.3
通讯作者：
Gu Y
中科院分区：
文献类型：
--
作者：
Qin Q;Niu J;Wang Z;Xu W;Qiao Z;Gu Y
晚期糖基化终产物(AGEs)、炎性相关巨噬细胞的迁移和聚集在糖尿病血管并发症的发生和发展中起关键作用。乙酰肝素酶(HPA)的酶活性与转移的肿瘤细胞和免疫系统的细胞的扩散密切相关。此外，HPA增强了包括AKT途径在内的特定信号分子的磷酸化，而不依赖于酶的活性。然而，目前对HPA在AGEs诱导的巨噬细胞迁移过程中所起的作用几乎一无所知。这些研究是在Ana-1巨噬细胞中进行的。用四甲基偶氮唑蓝((3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)比色法测定巨噬细胞活性。免疫印迹法检测巨噬细胞HPA和AKT蛋白的表达，实时定量RT-PCR检测HPA基因的表达。用双抗体夹心法测定HPA的释放量。用Transwell法检测巨噬细胞的迁移情况。AGEs处理的巨噬细胞HPA蛋白和mRNA显著增加。用识别HPA非酶末端的抗HPA抗体预处理可阻止AGEs诱导的AKT磷酸化和巨噬细胞迁移。PI3K/AKT抑制剂LY294002抑制AGEs诱导的巨噬细胞迁移。此外，用晚期糖基化终产物受体(RAGE)抗体预处理可减弱AGEs诱导的HPA表达、AKT磷酸化和巨噬细胞迁移。这些结果表明，AGEs诱导的巨噬细胞迁移依赖于涉及RAGE-HPA-PI3K/AKT通路的HPA。HPA的非酶活性可能在AGEs诱导的巨噬细胞迁移与糖尿病血管并发症的炎症相关中起关键作用。
Advanced glycation end products (AGEs), inflammatory-associated macrophage migration and accumulation are crucial for initiation and progression of diabetic vascular complication. Enzymatic activity of heparanase (HPA) is implicated strongly in dissemination of metastatic tumor cells and cells of the immune system. In addition, HPA enhances the phosphorylation of selected signaling molecules including AKT pathway independent of enzymatic activity. However, virtually nothing is presently known the role of HPA during macrophage migration exposed to AGEs involving signal pathway. These studies were carried out in Ana-1 macrophages. Macrophage viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. HPA and AKT protein expression in macrophages are analysed by Western blotting and HPA mRNA expression by real time quantitative RT-PCR. Release of HPA was determined by ELISA. Macrophage migration was assessed by Transwell assays. HPA protein and mRNA were found to be increased significantly in AGEs-treated macrophages. Pretreatment with anti-HPA antibody which recognizes the nonenzymatic terminal of HPA prevented AGEs-induced AKT phosphorylation and macrophage migration. LY294002 (PI3k/AKT inhibitor) inhibited AGEs-induced macrophage migration. Furthermore, pretreatment with anti-receptor for advanced glycation end products (RAGE) antibody attenuated AGEs-induced HPA expression, AKT phosphorylation and macrophage migration. These data indicate that AGEs-induced macrophage migration is dependent on HPA involving RAGE-HPA-PI3K/AKT pathway. The nonenzymatic activity of HPA may play a key role in AGEs-induced macrophage migration associated with inflammation in diabetic vascular complication.
登录
查看更多内容
影响因子：
7.7
作者：
Coughlan MT;Yap FY;Tong DC;Andrikopoulos S;Gasser A;Thallas-Bonke V;Webster DE;Miyazaki J;Kay TW;Slattery RM;Kaye DM;Drew BG;Kingwell BA;Fourlanos S;Groop PH;Harrison LC;Knip M;Forbes JM
通讯作者：
Forbes JM
影响因子：
7.7
作者：
Monden M;Koyama H;Otsuka Y;Morioka T;Mori K;Shoji T;Mima Y;Motoyama K;Fukumoto S;Shioi A;Emoto M;Yamamoto Y;Yamamoto H;Nishizawa Y;Kurajoh M;Yamamoto T;Inaba M
通讯作者：
Inaba M
RAGE 通过协同 ERK 激活介导机械应力和 AGE 联合诱导的加速糖尿病静脉移植物动脉粥样硬化
影响因子：
3.7
作者：
Li Y;Liu S;Zhang Z;Xu Q;Xie F;Wang J;Ping S;Li C;Wang Z;Zhang M;Huang J;Chen D;Hu L;Li C
通讯作者：
Li C
影响因子：
7.7
作者：
Reiniger N;Lau K;McCalla D;Eby B;Cheng B;Lu Y;Qu W;Quadri N;Ananthakrishnan R;Furmansky M;Rosario R;Song F;Rai V;Weinberg A;Friedman R;Ramasamy R;D'Agati V;Schmidt AM
通讯作者：
Schmidt AM
影响因子：
4.1
作者：
Boudot, Cedric;Saidak, Zuzana;Kamel, Said
通讯作者：
Kamel, Said