Diabetes disrupts the response of retinal endothelial cells to the angiomodulator lysophosphatidic acid.
Diabetes disrupts the response of retinal endothelial cells to the angiomodulator lysophosphatidic acid.
复制标题
DOI：
10.2337/db11-1189
复制
发表时间：
2012-05
期刊：
影响因子：
7.7
通讯作者：
Kazlauskas A
中科院分区：
文献类型：
--
作者：
Aranda J;Motiejunaite R;Im E;Kazlauskas A
本研究旨在探讨糖尿病（DM）对视网膜新生血管对溶血磷脂酸（LPA）反应性的影响及其机制。为此，我们使用了离体测定，其中当在两层胶原蛋白之间并且在血管内皮生长因子-A的存在下培养时，从视网膜外植体（从对照或DM小鼠分离）萌发新血管。虽然DM对新生血管的形成没有影响，但它阻止了LPA诱导的消退。高葡萄糖（HG）处理视网膜外植体模仿DM表型。同样，原代视网膜内皮细胞（RECs），这是经过HG处理，组织成管抗LPA。HG通过升高ROS引起RECs内的LPA抗性，ROS激活Src家族激酶，Src家族激酶刺激细胞外信号相关激酶（Erk）通路，Erk通路拮抗LPA介导的信号传导事件，而这些信号传导事件是消退所必需的。这一ROS/Src/Erk通路机制似乎与DM诱导视网膜新生血管LPA抵抗的途径相同。我们的结论是，DM/HG重新编程信号通路在RECs诱导LPA耐药的状态。
The objectives of this study were to investigate how diabetes mellitus (DM) influences responsiveness of retinal neovessels to lysophosphatidic acid (LPA) and to elucidate the underlying mechanism. To this end, we used an ex vivo assay in which neovessels sprouted from retinal explants (isolated from either control or DM mice) when cultured between two layers of collagen and in the presence of vascular endothelial growth factor-A. While DM had no effect on the formation of neovessels, it prevented LPA-induced regression. High-glucose (HG) treatment of retinal explants mimicked the DM phenotype. Similarly, primary retinal endothelial cells (RECs), which were subjected to HG treatment, organized into tubes that were resistant to LPA. HG caused LPA resistance within RECs by elevating ROS, which activated Src-family kinases that stimulated the extracellular signal–related kinase (Erk) pathway, which antagonized LPA-mediated signaling events that were required for regression. This ROS/Src/Erk pathway mechanism appeared to be the same route by which DM induced LPA resistance of retinal neovessels. We conclude that DM/HG reprograms signaling pathways in RECs to induce a state of LPA resistance.
登录
查看更多内容
DOI：
10.1056/nejmoa1001288
发表时间：
2010-07-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
ACCORD Study Group;ACCORD Eye Study Group;Chew EY;Ambrosius WT;Davis MD;Danis RP;Gangaputra S;Greven CM;Hubbard L;Esser BA;Lovato JF;Perdue LH;Goff DC Jr;Cushman WC;Ginsberg HN;Elam MB;Genuth S;Gerstein HC;Schubart U;Fine LJ
通讯作者：
Fine LJ
影响因子：
9.8
作者：
Elayappan, Banumathi;Ravinarayannan, Haribalaganesh;Gurunathan, Sangiliyandi
通讯作者：
Gurunathan, Sangiliyandi
影响因子：
11.4
作者：
Im, Eunok;Kazlauskas, Andrius
通讯作者：
Kazlauskas, Andrius
影响因子：
1.7
作者：
Mirshahi, A.;Roohipoor, R.;Faghihi, H.
通讯作者：
Faghihi, H.
影响因子：
82.9
作者：
通讯作者：
--