Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) Is Required for Branching Morphogenesis in the Chorioallantoic Placenta

Hiroyuki Tanaka; Koki Nagaike; Naoki Takeda; Hiroshi Itoh; Kazuyo Kohama; Tsuyoshi Fukushima; Shiro Miyata; Shuichiro Uchiyama; Shunro Uchinokura; Takeshi Shimomura; Keiji Miyazawa; Naomi Kitamura; Gen Yamada; Hiroaki Kataoka

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Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) Is Required for Branching Morphogenesis in the Chorioallantoic Placenta

机译：绒毛膜尿囊胎盘中的分支形态发生需要肝细胞生长因子激活剂抑制剂1（HAI-1）。

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Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-associated Kunitz-type serine proteinase inhibitor that was initially identified as a potent inhibitor of hepatocyte growth factor activator. HAI-1 is also a cognate inhibitor of matriptase, a membrane-associated serine proteinase. HAI-1 is expressed predominantly in epithelial cells in the human body. Its mRNA is also abundant in human placenta, with HAI-1 specifically expressed by villous cytotrophoblasts. In order to address the precise roles of HAI-1 in vivo, we generated HAI-1 mutant mice by homozygous recombination. Heterozygous HAI-1+/? mice underwent normal organ development. However, homozygous HAI-1?/? mice experienced embryonic lethality which became evident at embryonic day 10.5 postcoitum (E10.5). As early as E9.5, HAI-1?/? embryos showed growth retardation that did not reflect impaired cell proliferation but resulted instead from failed placental development and function. Histological analysis revealed severely impaired formation of the labyrinth layer, in contrast all other placental layers, such as the spongiotrophoblast layer and giant cell layer, which were formed. Our results indicate that mouse HAI-1 is essential for branching morphogenesis in the chorioallantoic placenta and lack of HAI-1 function may result in placental failure.

机译：肝细胞生长因子激活剂抑制剂1型（HAI-1）是一种与膜相关的Kunitz型丝氨酸蛋白酶抑制剂，最初被确定为肝细胞生长因子激活剂的有效抑制剂。 HAI-1还是matriptase的同源抑制剂，matriptase是一种与膜相关的丝氨酸蛋白酶。 HAI-1主要在人的上皮细胞中表达。它的mRNA在人胎盘中也很丰富，HAI-1由绒毛细胞滋养细胞特异性表达。为了解决HAI-1在体内的确切作用，我们通过纯合重组产生了HAI-1突变小鼠。杂合子 HAI-1 + /？小鼠器官发育正常。但是，纯合子 HAI-1 ？/？小鼠经历了胚胎致死率，在死后10.5天（E10.5）变得明显。早在E9.5时， HAI-1 ？/？胚胎就显示出生长迟缓，这并不反映细胞增殖受损，而是胎盘发育和功能衰竭所致。组织学分析显示，迷宫层的形成受到严重损害，相比之下，形成的所有其他胎盘层，例如海绵状滋养层和巨细胞层。我们的结果表明，小鼠HAI-1对于绒膜尿囊胎盘中的分支形态发生至关重要，缺乏HAI-1功能可能会导致胎盘衰竭。 展开▼

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《Molecular and Cellular Biology》 |2005年第13期|共12页

作者
Hiroyuki Tanaka; Koki Nagaike; Naoki Takeda; Hiroshi Itoh; Kazuyo Kohama; Tsuyoshi Fukushima; Shiro Miyata; Shuichiro Uchiyama; Shunro Uchinokura; Takeshi Shimomura; Keiji Miyazawa; Naomi Kitamura; Gen Yamada; Hiroaki Kataoka;
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中图分类细胞生物学;

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1. Defect of hepatocyte growth factor activator inhibitor type 1/serine protease inhibitor, Kunitz type 1 (Hai-1/Spint1) leads to ichthyosis-like condition and abnormal hair development in mice. [J] . Nagaike K, Kawaguchi M, Takeda N, American Journal of Pathology: Official Publication of the American Association of Pathologists . 2008,第5期

机译：肝细胞生长因子激活剂抑制剂1型/丝氨酸蛋白酶抑制剂1型，库尼兹1型（Hai-1 / Spint1）的缺陷会导致鱼鳞病样状况和小鼠毛发发育异常。

2. Engineering a potent inhibitor of matriptase from the natural hepatocyte growth factor activator inhibitor type-1 (HAI-1) protein [J] . Aaron Mitchell, Deepti Kannan, Sean Hunter, The Journal of biological chemistry . 2018,第14期

机译：从天然肝细胞生长因子激活剂抑制剂1型（HAI-1）蛋白中设计一种有效的抗Matriptase的抑制剂

3. Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) * [J] . Marybeth Sechler, Stanley Borowicz, Michelle Van Scoyk, The Journal of biological chemistry . 2015,第25期

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4. Plasminogen activator inhibitor -1 and vascular endothelial growth factor as risk factors for early prediction of gestational diabetes [C] . Elksne K., Paunina Z., Jurka A., European Congress of Obstetrics and Gynaecology . 2012

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6. Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) Is Required for Branching Morphogenesis in the Chorioallantoic Placenta [O] . Hiroyuki Tanaka, Koki Nagaike, Naoki Takeda, 2005

机译：绒毛膜尿囊胎盘中的分支形态发生需要肝细胞生长因子激活因子抑制剂1（HAI-1）。

7. Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) Is Required for Branching Morphogenesis in the Chorioallantoic Placenta [O] . Tanaka, Hiroyuki, Nagaike, Koki, Takeda, Naoki, 2005

机译：绒毛膜尿囊胎盘中的分支形态发生需要肝细胞生长因子激活因子抑制剂1（HAI-1）。

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机译：多肽，特异性结合剂，核酸分子和分离的细胞系，宿主细胞，组合物和抗原结合域或抗体，以及治疗患者癌症和实体瘤，检测样品中生长因子水平的肝细胞（hgf），获得抗体的方法并抑制hgf与met的结合并降低或防止任何肝细胞生长因子（hgf）特异性结合剂的结合

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Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) Is Required for Branching Morphogenesis in the Chorioallantoic Placenta

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