Smad signaling pathways regulate pancreatic endocrine development.
Smad signaling pathways regulate pancreatic endocrine development.
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DOI：
10.1016/j.ydbio.2013.04.003
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发表时间：
2013-06-15
影响因子：
2.7
通讯作者：
Gittes, George
中科院分区：
文献类型：
--
作者：
El-Gohary, Yousef;Tulachan, Sidhartha;Guo, Ping;Welsh, Carey;Wiersch, John;Prasadan, Krishna;Paredes, Jose;Shiota, Chiyo;Xiao, Xiangwei;Wada, Yoko;Diaz, Marilyn;Gittes, George
胰腺内分泌细胞群的扩增发生在胚胎发育期间以及出生后胰腺生长和再生期间。胚胎发育过程中内分泌细胞扩增的机制尚未完全了解，并且胚胎内分泌胰腺的生长与成年动物中发生的胰岛细胞复制之间尚未建立明确的机制联系。我们发现转化生长因子-β（TGF-β）超家族信号传导参与许多发育过程，在调节胰腺内分泌成熟和发育中发挥着关键作用。具体而言，TGF-β 信号传导的细胞内介质 smad2 和 smad3 及其抑制剂 smad7 似乎介导了这一过程。 Smad2、smad3 和 smad7 均在早期胚胎胰腺上皮细胞中广泛表达。然而，在发育后期，smad2 和 smad3 强烈定位于内分泌阳性细胞的细胞核，而抑制性 smad7 在内分泌成分中消失。 smad2和smad3的基因失活导致胚胎内分泌室显着扩张，而smad7的基因失活导致内分泌室显着减少。体外反义研究进一步证实了这些结果，并支持抑制性 smad7 和细胞内介质 smad2/3 之间的相互作用是胰腺内分泌发育的控制点的可能性。这些结果应该有助于更好地理解 β 细胞发育的关键控制机制。
Expansion of the pancreatic endocrine cell population occurs during both embryonic development and during post-natal pancreatic growth and regeneration. Mechanisms of the expansion of endocrine cells during embryonic development are not completely understood, and no clear mechanistic link has been established between growth of the embryonic endocrine pancreas and the islet cell replication that occurs in an adult animal. We found that transforming growth factor-beta (TGF-β) superfamily signaling, which has been implicated in many developmental processes, plays a key role in regulating pancreatic endocrine maturation and development. Specifically, the intracellular mediators of TGF-β signaling, smad2 and smad3, along with their inhibitor smad7, appear to mediate this process. Smad2, smad3 and smad7 were all broadly expressed throughout the early embryonic pancreatic epithelium. However, during later stages of development, smad2 and smad3 became strongly localized to the nuclei of the endocrine positive cells, whereas the inhibitory smad7 became absent in the endocrine component. Genetic inactivation of smad2 and smad3 led to a significant expansion of the embryonic endocrine compartment, whereas genetic inactivation of smad7 led to a significant decrease in the endocrine compartment. In vitro antisense studies further corroborated these results and supported the possibility that interplay between the inhibitory smad7 and the intracellular mediators smad2/3 is a control point for pancreatic endocrine development. These results should provide a better understanding of the key control mechanisms for β-cell development.
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影响因子：
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