Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy.
Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy.
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周细胞迁移：实验性糖尿病性视网膜病中周细胞丧失的一种新型机制。
DOI：
10.2337/db08-0325
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发表时间：
2008-09
期刊：
影响因子：
7.7
通讯作者：
Hammes, Hans-Peter
中科院分区：
文献类型：
--
作者：
Pfister, Frederick;Feng, Yuxi;Hagen, Franziska Vom;Gans, Rijk;Deutsch, Urban;Hammes, Hans-Peter
目的-早期糖尿病视网膜病变期间周细胞损失的潜在机制仍然存在争议。高血压诱导血管生成素-2（Ang-2）转录，其调节毛细血管周细胞覆盖。在这项研究中，我们评估了周细胞亚群的损失和Ang-2对周细胞迁移的贡献。研究设计和方法-在自发性糖尿病XLacZ小鼠的视网膜消化物制备物中定量总周细胞及其亚群的数量。周细胞被分为亚组，根据其定位，其位置相对于相邻的内皮细胞，和LacZ的表达。在Ang-2过表达（mOpsinhAng 2）和缺陷（Ang 2LacZ）小鼠中评估Ang-2对周细胞迁移的贡献。结果：糖尿病6个月后，XLacZ小鼠的周细胞数减少了16%（P < 0.01）.周细胞减少仅限于直毛细血管上的周细胞（相对减少27%，P < 0.05），主要见于LacZ阳性周细胞（-20%，P < 0.01）。高血压增加了迁移的周细胞的数量（69%; P < 0.05），其中由于糖尿病引起的相对增加仅在LacZ阴性的周细胞中，表明对毛细血管的粘附减少（176%; P < 0.01）。非糖尿病视网膜中Ang-2的过度表达与野生型动物的糖尿病周细胞迁移相似（78%; P < 0.01）。与野生型同窝小鼠相比，Ang-2缺陷小鼠完全没有高血糖诱导的周细胞迁移增加。结论：糖尿病周细胞丢失是周细胞迁移的结果，这一过程是由Ang-Tie系统调节的。
OBJECTIVE— The mechanism underlying pericyte loss during incipient diabetic retinopathy remains controversial. Hyperglycemia induces angiopoietin-2 (Ang-2) transcription, which modulates capillary pericyte coverage. In this study, we assessed loss of pericyte subgroups and the contribution of Ang-2 to pericyte migration. RESEARCH DESIGN AND METHODS— Numbers of total pericytes and their subgroups were quantified in retinal digest preparations of spontaneous diabetic XLacZ mice. Pericytes were divided into subgroups according to their localization, their position relative to adjacent endothelial cells, and the expression of LacZ. The contribution of Ang-2 to pericyte migration was assessed in Ang-2 overexpressing (mOpsinhAng2) and deficient (Ang2LacZ) mice. RESULTS— Pericyte numbers were reduced by 16% (P < 0.01) in XLacZ mice after 6 months of diabetes. Reduction of pericytes was restricted to pericytes on straight capillaries (relative reduction 27%, P < 0.05) and was predominantly observed in LacZ-positive pericytes (−20%, P < 0.01). Hyperglycemia increased the numbers of migrating pericytes (69%; P < 0.05), of which the relative increase due to diabetes was exclusively in LacZ-negative pericytes, indicating reduced adherence to the capillaries (176%; P < 0.01). Overexpression of Ang-2 in nondiabetic retinas mimicked diabetic pericyte migration of wild-type animals (78%; P < 0.01). Ang-2 deficient mice completely lacked hyperglycemia-induced increase in pericyte migration compared with wild-type littermates. CONCLUSIONS— Diabetic pericyte loss is the result of pericyte migration, and this process is modulated by the Ang-Tie system.