ISL1 promotes pancreatic islet cell proliferation.
ISL1 promotes pancreatic islet cell proliferation.
复制标题
ISL1 促进胰岛细胞增殖。
DOI：
10.1371/journal.pone.0022387
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zhou C
中科院分区：
文献类型：
--
作者：
Guo T;Wang W;Zhang H;Liu Y;Chen P;Ma K;Zhou C
胰岛1（Islet 1，ISL 1）是一种LIM同源域转录因子，在胚胎和出生后的胰岛中，对促进胰岛增殖和维持内分泌细胞存活至关重要。然而，到目前为止，ISL 1如何在成人胰岛中发挥作用尚不清楚。我们的研究结果表明，ISL 1的表达上调，无论是在培养的胰腺细胞经历葡萄糖氧化酶刺激，以及在1型和2型糖尿病小鼠模型的mRNA水平。ISL 1基因表达下调可增加HIT-T15胰岛细胞的凋亡水平。以HIT-T15和原代成人胰岛细胞为细胞模型，我们发现ISL 1促进成人胰岛细胞增殖，增加c-Myc和CyclinD 1的转录，而敲低ISL 1则增加G1期细胞的比例，减少G2/M和S期细胞的比例。进一步的研究表明，ISL 1通过直接结合c-Myc和CyclinD 1的启动子来激活它们的转录。ISL 1促进成人胰岛细胞增殖，可能通过直接结合c-Myc和CyclinD 1的启动子激活其转录。我们的发现扩展了关于ISL 1在维持成熟胰岛细胞稳态中的关键作用的知识。我们的研究结果也提供了新的调控关系ISL 1和其他生长因子的见解。
Islet 1 (ISL1), a LIM-homeodomain transcription factor is essential for promoting pancreatic islets proliferation and maintaining endocrine cells survival in embryonic and postnatal pancreatic islets. However, how ISL1 exerts the role in adult islets is, to date, not clear. Our results show that ISL1 expression was up-regulated at the mRNA level both in cultured pancreatic cells undergoing glucose oxidase stimulation as well in type 1 and type 2 diabetes mouse models. The knockdown of ISL1 expression increased the apoptosis level of HIT-T15 pancreatic islet cells. Using HIT-T15 and primary adult islet cells as cell models, we show that ISL1 promoted adult pancreatic islet cell proliferation with increased c-Myc and CyclinD1 transcription, while knockdown of ISL1 increased the proportion of cells in G1 phase and decreased the proportion of cells in G2/M and S phases. Further investigation shows that ISL1 activated both c-Myc and CyclinD1 transcription through direct binding on their promoters. ISL1 promoted adult pancreatic islet cell proliferation and probably by activating c-Myc and CyclinD1 transcription through direct binding on their promoters. Our findings extend the knowledge about the crucial role of ISL1 in maintaining mature islet cells homeostasis. Our results also provide insights into the new regulation relationships between ISL1 and other growth factors.
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