All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas.
All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas.
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DOI：
10.2337/diabetes.52.1.76
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发表时间：
2003
期刊：
影响因子：
7.7
通讯作者：
S. Tulachan;R. Doi;Y. Kawaguchi;S. Tsuji;S. Nakajima;T. Masui;M. Koizumi;E. Toyoda;Tomohiko Mori;D. Ito;K. Kami;K. Fujimoto;M. Imamura
中科院分区：
文献类型：
--
作者：
S. Tulachan;R. Doi;Y. Kawaguchi;S. Tsuji;S. Nakajima;T. Masui;M. Koizumi;E. Toyoda;Tomohiko Mori;D. Ito;K. Kami;K. Fujimoto;M. Imamura
在胚胎期，维甲酸作为间充质诱导剂在许多器官中发挥作用，包括肾脏、肺、中枢神经系统和肠道。维甲酸(RA)在成人胰腺中具有促胰岛素作用，但仅有有限的研究阐明其在胰腺器官发生中的作用。在这项研究中，我们分析了胚胎胰腺中RA信号机制的存在，并通过体外组织培养实验评估了它的作用。在这里，我们展示了胚胎胰腺组织中存在内源性视黄醛脱氢酶2(RALDH2)，最有效的RA合成酶，RA结合蛋白和RA受体(RARs)。RALDH2仅在间充质中表达。在组织培养实验中加入外源性全反式维甲酸(AtRA)，刺激内分泌细胞和导管细胞分化，促进腺泡组织细胞凋亡。此外，我们还证明atRA上调了PDX-1的表达。综上所述，我们的研究结果表明，全反式维甲酸介导的间充质/上皮细胞之间的相互作用通过调节PDX-1基因在决定上皮细胞命运中发挥重要作用，从而导致胰腺器官发生过程中内分泌和外分泌成分的正确形成。
Retinoids during the embryonic period act as a mesenchymal inducer in many organs, including kidney, lung, central nervous system, and gut. Retinoic acid (RA) demonstrates insulinotropic effects in adult pancreas, but only a limited study has elucidated its role in pancreatic organogenesis. In this study, we have analyzed the existence of RA-signaling machinery in embryonic pancreas and evaluated its role using in vitro tissue culture experiments. Here we show the presence of endogenous retinaldehyde dehydrogenase 2 (RALDH2), the most effective RA-synthesizing enzyme, RA-binding proteins, and RA receptors (RARs) in embryonic pancreatic tissue. RALDH2 is expressed exclusively in the mesenchyme. Exogenously added all-trans-retinoic acid (atRA) in tissue culture experiments stimulated differentiation of endocrine and duct cells and promoted apoptotic cell death of acinar tissue. Furthermore, we demonstrate that atRA upregulates the PDX-1 expression. Taken together, our data suggest that atRA-mediated mesenchymal/epithelial interactions play an important role in determining the cell fate of epithelial cells via regulation of the PDX-1 gene, leading to the proper formation of the endocrine versus exocrine component during pancreatic organogenesis.