Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model
Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model
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DOI：
10.1007/s00125-017-4254-y
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发表时间：
2017-07-01
期刊：
影响因子：
8.2
通讯作者：
Hammes, Hans-Peter
中科院分区：
文献类型：
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作者：
Friedrichs, Patrick;Schlotterer, Andrea;Hammes, Hans-Peter
目的/假说本研究的目的是评价高血糖记忆小鼠模型对神经血管单位的损伤。方法采用链脲佐菌素诱导的小鼠糖尿病模型(C57BL/6J背景)，采用胰岛素释放小球和胰岛细胞移植。结果视网膜血管周细胞持续丢失(pC/mm(2))：与健康对照组(1981+/-404pC/mm(2))相比，糖尿病小鼠视网膜血管周细胞覆盖率(1571+/-383pC/mm(2)，p<；0.001)和移植小鼠(1606+/-268 pC/mm(2)，p<；0.001)显著减少。符合高血糖记忆标准的基因被归因于神经血管单位的细胞骨架和核细胞隔间。在细胞骨架中最显著的调控基因是Ddx51、Fgd4、Pdlim7、Utp23、Cep57、Csrp3、Em15、Fhl3、Map1a、Mapk1ip1、MNDA、Neil2、Parp2、Myl12b、dyll1、Stag3和Sntg2，而在核中最显著的调控基因是Ddx51、Utp23、MNDA、Kmt2e、Nr6a1、Parp2、CDK8、SRSF1和Zfp326。数据可用性本研究期间生成和/或分析的数据集可在GEO存储库中获得，GSE87433，www.ncbi.nlm.nih.gov/geo/Query/acc.cgi？Token=idmbysgctLuxviv&acc=GSE87433。
Aims/hypothesis The aim of this study was to evaluate damage to the neurovascular unit in a mouse model of hyperglycaemic memory.Methods A streptozotocin-induced mouse model of diabetes (C57BL/6J background) received insulin-releasing pellets and pancreatic islet-cell transplantation. Damage to the neurovascular unit was studied by quantitative retinal morphometry for microvascular changes and microarray analysis, with subsequent functional annotation clustering, for changes of the retinal genome.Results Sustained microvascular damage was confirmed by persistent loss of pericytes in the retinal vasculature (PC/mm(2)): compared with healthy controls (1981 +/- 404 PC/mm(2)), the pericyte coverage of the retinal vasculature was significantly reduced in diabetic mice (1571 +/- 383 PC/mm(2), p < 0.001) and transplanted mice (1606 +/- 268 PC/mm(2), p < 0.001). Genes meeting the criteria for hyperglycaemic memory were attributed to the cytoskeletal and nuclear cell compartments of the neurovascular unit. The most prominent regulated genes in the cytoskeletal compartment were Ddx51, Fgd4, Pdlim7, Utp23, Cep57, Csrp3, Eml5, Fhl3, Map1a, Mapk1ip1, Mnda, Neil2, Parp2, Myl12b, Dynll1, Stag3 and Sntg2, and in the nuclear compartment were Ddx51, Utp23, Mnda, Kmt2e, Nr6a1, Parp2, Cdk8, Srsf1 and Zfp326.Conclusions/interpretation We demonstrated that changes in gene expression and microvascular damage persist after euglycaemic re-entry, indicating memory. Data availability The datasets generated during and/or analysed during the current study are available in the GEO repository, GSE87433, www.ncbi.nlm.nih.gov/geo/query/acc.cgi? token=idmbysgctluxviv&acc=GSE87433.