PDF(Pubmed)
Abstract：
Non-obese diabetes (NOD) mice are an established, spontaneous model of type 1 diabetes in which diabetes develops through insulitis. Using next-generation sequencing, coupled with pathway analysis, the molecular fingerprint of early insulitis was mapped in a cohort of mice ranging from 4 to 12 weeks of age. The resulting dynamic timeline revealed an initial decrease in proliferative capacity followed by the emergence of an inflammatory signature between 6 and 8 weeks that increased to a regulatory plateau between 10 and 12 weeks. The inflammatory signature is identified by the activation of central immunogenic factors such as Infg, Il1b, and Tnfa, and activation of canonical inflammatory signaling. Analysis of the regulatory landscape revealed the transcription factor Atf3 as a potential novel modulator of inflammatory signaling in the NOD islets. Furthermore, the Hedgehog signaling pathway correlated with Atf3 regulation, suggesting that the two play a role in regulating islet inflammation; however, further studies are needed to establish the nature of this connection.
摘要：
非肥胖糖尿病(NOD)小鼠是一种既定的，自发的1型糖尿病模型，其中糖尿病通过胰岛炎发展。使用下一代测序，加上途径分析，早期胰岛炎的分子指纹图谱在一组4~12周龄的小鼠中绘制.所得的动态时间线显示增殖能力的初始降低,随后在6至8周之间出现炎性特征,其在10至12周之间增加至调节平台。通过激活中枢免疫原性因子如Infg，Il1b,还有Tnfa,和典型炎症信号的激活。对调控景观的分析揭示了转录因子Atf3作为NOD胰岛中炎症信号传导的潜在新型调节剂。此外，Hedgehog信号通路与Atf3调节相关，这表明两者在调节胰岛炎症中起作用；然而，需要进一步的研究来确定这种联系的性质。
