A smad signaling network regulates islet cell proliferation.
A smad signaling network regulates islet cell proliferation.
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作者：
El-Gohary Y;Tulachan S;Wiersch J;Guo P;Welsh C;Prasadan K;Paredes J;Shiota C;Xiao X;Wada Y;Diaz M;Gittes G
胰腺β细胞损失和功能障碍是所有类型糖尿病的关键组成部分。人类和啮齿动物的β细胞能够增殖，这种增殖是对抗糖尿病演变和进展的重要防御。转化生长因子-β（TGF-β）信号传导已显示影响β细胞发育、增殖和功能，但β细胞增殖被认为是成人中新β细胞的唯一来源。最近，β细胞去分化已被证明是β细胞衰竭的重要促成机制。在这项研究中，我们通过显示细胞内TGF-β调节剂smads 7，2和3的网络将这两种途径联系在一起，在β细胞损失后控制β细胞增殖，特别是smads 7对于β细胞增殖是必需的。重要的是，这种smad 7介导的增殖似乎需要通过β细胞的短暂的非病理性去分化，以达到胰腺多肽折叠的阳性状态。TGF-β受体II似乎是控制β细胞中smad网络状态的重要受体。这些研究应该有助于我们理解β细胞复制的正确调控。
Pancreatic β-cell loss and dysfunction are critical components of all types of diabetes. Human and rodent β-cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor-β (TGF-β) signaling has been shown to affect β-cell development, proliferation, and function, but β-cell proliferation is thought to be the only source of new β-cells in the adult. Recently, β-cell dedifferentiation has been shown to be an important contributory mechanism to β-cell failure. In this study, we tie together these two pathways by showing that a network of intracellular TGF-β regulators, smads 7, 2, and 3, control β-cell proliferation after β-cell loss, and specifically, smad7 is necessary for that β-cell proliferation. Importantly, this smad7-mediated proliferation appears to entail passing through a transient, nonpathologic dedifferentiation of β-cells to a pancreatic polypeptide–fold hormone-positive state. TGF-β receptor II appears to be a receptor important for controlling the status of the smad network in β-cells. These studies should help our understanding of properly regulated β-cell replication.
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影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA
影响因子：
56.9
作者：
LIKE, AA;CHICK, WL
通讯作者：
CHICK, WL
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
30.8
作者：
Kawaguchi, Y;Cooper, B;Wright, CVE
通讯作者：
Wright, CVE
影响因子：
15.9
作者：
Georgia, S;Bhushan, A
通讯作者：
Bhushan, A