Smad Proteins and Hepatocyte Growth Factor Control Parallel Regulatory Pathways That Converge on β1-Integrin To Promote Normal Liver Development

Michael Weinstein; Satdarshan P. S. Monga; Ye Liu; Steven G. Brodie; Yi Tang; Cuiling Li; Lopa Mishra; Chu-Xia Deng

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Smad Proteins and Hepatocyte Growth Factor Control Parallel Regulatory Pathways That Converge on β1-Integrin To Promote Normal Liver Development

机译：Smad蛋白和肝细胞生长因子控制在β1-整合素上聚集的促进肝正常发育的平行调节途径。

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Smads serve as intracellular mediators of transforming growth factor β (TGF-β) signaling. After phosphorylation by activated type I TGF-β receptors, Smad proteins translocate to the nucleus, where they serve as transcription factors and increase or decrease expression of TGF-β target genes. Mice lacking one copy each ofSmad2 and Smad3 suffered midgestation lethality due to liver hypoplasia and anemia, suggesting essential dosage requirements of TGF-β signal components. This is likely due to abnormal adhesive properties of the mutant hepatocytes, which may result from a decrease in the level of the β1-integrin and abnormal processing and localization of E-cadherin. Culture of mutant livers in vitro revealed the existence of a parallel developmental pathway mediated by hepatocyte growth factor (HGF), which could rescue the mutant phenotype independent of Smad activation. These pathways merge at the β1-integrin, the level of which was increased by HGF in the cultured mutant livers. HGF treatment reversed the defects in cell proliferation and hepatic architecture in theSmad2 +/? ; Smad3 +/? livers.

机译：Smads充当转化生长因子β（TGF-β）信号传导的细胞内介体。在被激活的I型TGF-β受体磷酸化后，Smad蛋白易位至核，在核中充当转录因子并增加或减少TGF-β靶基因的表达。分别缺乏 Smad2 和 Smad3 一份的小鼠由于肝脏发育不全和贫血而发生了中期致死性，提示TGF-β信号成分的基本剂量要求。这可能是由于突变型肝细胞的异常粘附特性所致，这可能是由于β1-整合素水平的下降以及E-钙粘蛋白的异常加工和定位所致。体外培养突变肝显示出存在由肝细胞生长因子（HGF）介导的平行发育途径，该途径可以拯救独立于Smad激活的突变表型。这些途径在β1-整合素处合并，β1整合素的水平在培养的突变肝中被HGF所增加。 HGF处理逆转了 Smad2 + /？ 中细胞增殖和肝结构的缺陷; Smad3 + /？肝脏。 展开▼

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《Molecular and Cellular Biology》 |2001年第15期|共10页

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Michael Weinstein; Satdarshan P. S. Monga; Ye Liu; Steven G. Brodie; Yi Tang; Cuiling Li; Lopa Mishra; Chu-Xia Deng;
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中图分类细胞生物学;

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1. Mechanism of a transcriptional cross talk between transforming growth factor-beta-regulated Smad3 and Smad4 proteins and orphan nuclear receptor hepatocyte nuclear factor-4 [J] . Chou WC., Prokova V., Shiraishi K., Molecular biology of the cell . 2003,第3期

机译：转化生长因子β调控的Smad3和Smad4蛋白与孤儿核受体肝细胞核因子4之间的转录串扰的机制。

2. Protein engineered variants of hepatocyte growth factor/scatter factor promote proliferation of primary human hepatocytes and in rodent liver [J] . RossJ., GherardiE., MallorquifernandezN., Gastroenterology . 2012,第4期

机译：肝细胞生长因子/散射因子的蛋白质工程变体可促进人类原代肝细胞和啮齿动物肝脏的增殖

3. Increased miR-16 expression induced by hepatitis C virus infection promotes liver fibrosis through downregulation of hepatocyte growth factor and Smad7 [J] . Zhu Bin, Wei Xiao-xia, Wang Tian-bao, Archives of virology . 2015,第8期

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4. The Influence of Hepatocyte Growth-Promoting Factors Combined with Gongying Yinchen Soup for Depression in Patients with Fulminant Hepatitis Peripheral Blood T Lymphocyte Subsets and Liver Function [C] . Liping Wu, Junfeng Gao, Xinguo Zhao, International symposium on IT in medicine and education . 2014

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5. Analysis of progestin effects on hepatocyte growth factor signaling pathways in relation to proliferation and alveolar morphogenesis of normal mammary epithelial cell in vitro. [D] . Smith, Kyle Thomas. 2005

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6. Smad Proteins and Hepatocyte Growth Factor Control Parallel Regulatory Pathways That Converge on β1-Integrin To Promote Normal Liver Development [O] . Michael Weinstein, Satdarshan P. S. Monga, Ye Liu, 2001

机译：Smad蛋白和肝细胞生长因子控制在β1整合素上聚集的促进肝正常发育的平行调节途径。

7. Smad Proteins and Hepatocyte Growth Factor Control Parallel Regulatory Pathways That Converge on β1-Integrin To Promote Normal Liver Development [O] . Weinstein, Michael, Monga, Satdarshan P. S., Liu, Ye, 2001

机译：Smad蛋白和肝细胞生长因子控制在β1整合素上聚集的促进肝正常发育的平行调节途径。

8. Analysis of Progestin Effects on Hepatocyte Growth Factor Signaling Pathways in Relation to Proliferation and Alveolar Morphogenesis of Normal Mammary Epithelial Cells in Vitro [R] . Smith, K. T. 2003

机译：孕激素对肝细胞生长因子信号通路的影响与体外正常乳腺上皮细胞增殖和肺泡形态发生的关系

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Smad Proteins and Hepatocyte Growth Factor Control Parallel Regulatory Pathways That Converge on β1-Integrin To Promote Normal Liver Development

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