Extracellular Matrix Modulates Insulin Production During Differentiation of AR42J Cells: Functional Role of Pax6 Transcription Factor
Extracellular Matrix Modulates Insulin Production During Differentiation of AR42J Cells: Functional Role of Pax6 Transcription Factor
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DOI：
10.1002/jcb.22930
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Kojima, Itaru
中科院分区：
文献类型：
--
作者：
Hamamoto, Kohei;Yamada, Satoko;Kojima, Itaru
细胞外基质 (ECM) 在发育过程中调节胰腺 β 细胞的分化。然而，ECM 蛋白调节分化的机制尚不完全清楚。我们研究了 ECM 蛋白对体外分化 β 细胞的影响。我们研究了基底膜 ECM 对 AR42J 细胞和大鼠导管细胞分化的影响。首先，我们检测了重组基底膜Matrigel 对激活素和βcellulin 诱导的AR42J 细胞分化的影响。 Matrigel 增强了胰岛素的产生并增加了 GLUT2、SUR1 和葡萄糖激酶的表达。在研究的各种转录因子中，Matrigel 显着上调 Pax6 的表达。当 Pax6 在用激活素和 betacellulin 处理的细胞中过度表达时，胰岛素的表达上调。相反，敲低 Pax6 显着降低基质胶上培养的细胞中的胰岛素表达。 Matrigel 对胰岛素产生和 Pax6 诱导的影响部分由 Matrigel 的主要成分 laminin-1 再现，并被抗整合素 β 1 抗体抑制。 Matrigel 还增强了由激活素和 betacellulin 诱导的 p38 丝裂原激活激酶的激活，而该激活被抗 β1 抗体抑制。最后，在大鼠培养的导管细胞中再现了Matrigel对分化的影响，并且Matrigel还增加了Pax6的表达。这些结果表明基底膜 ECM 通过上调 Pax6 的表达来增强胰腺祖细胞向胰岛素分泌细胞的分化。 J.细胞。生物化学。 112: 318329, 2011。(C) 2010 Wiley-Liss, Inc.
Extracellular matrix (ECM) modulates differentiation of pancreatic beta-cells during development. However, the mechanism by which ECM proteins modulate differentiation is not totally clear. We investigated the effect of ECM proteins on differentiation beta-cells in vitro. We investigated the effect of basement membrane ECM on differentiation of AR42J cells and rat ductal cells. First, we examined the effect of reconstituted basement membrane, Matrigel on differentiation of AR42J cells induced by activin and betacellulin. Matrigel augmented insulin production and increased the expression of GLUT2, SUR1, and glucokinase. Among various transcription factors investigated, Matrigel markedly upregulated the expression of Pax6. When Pax6 was overexpressed in cells treated with activin and betacellulin, the expression of insulin was upregulated. Conversely, knockdown of Pax6 significantly reduced the insulin expression in cells cultured on Matrigel. The effects of Matrigel on insulin-production and induction of Pax6 were reproduced partially by laminin-1, a major component of Matrigel, and inhibited by anti-integrin-beta 1 antibody. Matrigel also enhanced the activation of p38 mitogen-activated kinase induced by activin and betacellulin, which was inhibited by anti-beta 1 antibody. Finally, the effect of Matrigel on differentiation was reproduced in rat cultured ductal cells, and Matrigel also increased the expression of Pax6. These results indicate that basement membrane ECM augments differentiation of pancreatic progenitor cells to insulin-secreting cells by upregulating the expression of Pax6. J. Cell. Biochem. 112: 318329, 2011. (C) 2010 Wiley-Liss, Inc.