β-catenin is selectively required for the expansion and regeneration of mature pancreatic acinar cells in mice.
β-catenin is selectively required for the expansion and regeneration of mature pancreatic acinar cells in mice.
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DOI：
10.1242/dmm.007799
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发表时间：
2012-07
影响因子：
4.3
通讯作者：
Murtaugh LC
中科院分区：
文献类型：
--
作者：
Keefe MD;Wang H;De La O JP;Khan A;Firpo MA;Murtaugh LC
胰腺的大小由内在因素（如祖细胞的数量）和控制这些祖细胞的命运和增殖的外在信号决定。胰腺的外分泌和内分泌区室在出生后都经历了急剧的扩张，并且能够在损伤后至少部分再生。这些谱系的扩张是否依赖于类似的机制尚不清楚。虽然我们已经证明，Wnt信号组分β-catenin是选择性地需要在小鼠胚胎的外分泌腺泡细胞的产生，这种蛋白质已被归因于各种功能，在出生后的胰腺，包括增殖和再生的胰岛以及腺泡细胞。为了解决β-连环蛋白是否对成熟腺泡细胞的维持和扩增仍然重要，我们建立了一个系统来跟踪小鼠出生后生长和再生过程中β-连环蛋白缺陷细胞的行为和命运。我们发现，β-连环蛋白是持续需要的腺泡细胞质量的建立和维护，从胚胎规格通过青少年和成人的自我更新和再生。胰岛细胞不具有这种要求，胰岛细胞在缺乏β-连环蛋白的情况下正常增殖和发挥功能。这些结果对Wnt-β-catenin信号传导在人类内分泌和外分泌疾病的病因学中的相对作用做出了不同的预测。我们认为，Wnt-β-catenin活性的丧失不太可能导致胰岛功能障碍，如2型糖尿病，但β-catenin可能促进损伤后的人腺泡细胞增殖，因此可能有助于急性或慢性胰腺炎的解决。
The size of the pancreas is determined by intrinsic factors, such as the number of progenitor cells, and by extrinsic signals that control the fate and proliferation of those progenitors. Both the exocrine and endocrine compartments of the pancreas undergo dramatic expansion after birth and are capable of at least partial regeneration following injury. Whether the expansion of these lineages relies on similar mechanisms is unknown. Although we have shown that the Wnt signaling component β-catenin is selectively required in mouse embryos for the generation of exocrine acinar cells, this protein has been ascribed various functions in the postnatal pancreas, including proliferation and regeneration of islet as well as acinar cells. To address whether β-catenin remains important for the maintenance and expansion of mature acinar cells, we have established a system to follow the behavior and fate of β-catenin-deficient cells during postnatal growth and regeneration in mice. We find that β-catenin is continuously required for the establishment and maintenance of acinar cell mass, extending from embryonic specification through juvenile and adult self-renewal and regeneration. This requirement is not shared with islet cells, which proliferate and function normally in the absence of β-catenin. These results make distinct predictions for the relative role of Wnt–β-catenin signaling in the etiology of human endocrine and exocrine disease. We suggest that loss of Wnt–β-catenin activity is unlikely to drive islet dysfunction, as occurs in type 2 diabetes, but that β-catenin is likely to promote human acinar cell proliferation following injury, and might therefore contribute to the resolution of acute or chronic pancreatitis.
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DOI：
10.1073/pnas.0810111105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Jean-Paul, De La O.;Emerson, Lyska L.;Murtaugh, L. Charles
通讯作者：
Murtaugh, L. Charles
影响因子：
3.5
作者：
Le Bacquer, Olivier;Shu, Luan;Maedler, Kathrin
通讯作者：
Maedler, Kathrin
影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA
影响因子：
30.8
作者：
Kawaguchi, Y;Cooper, B;Wright, CVE
通讯作者：
Wright, CVE
DOI：
10.1073/pnas.0810097105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Habbe, Nils;Shi, Guanglu;Maitra, Anirban
通讯作者：
Maitra, Anirban