Estrogen‐dependent expression of the tissue kallikrein gene (Klk1) in the mouse uterus and its implications for endometrial tissue growth

Estrogen‐dependent expression of the tissue kallikrein gene (Klk1) in the mouse uterus and its implications for endometrial tissue growth
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DOI:
10.1002/mrd.20567
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发表时间:
2007-08
影响因子:
2.5
通讯作者:
S. Rajapakse;Noriko Yamano;K. Ogiwara;K. Hirata;Sumio Takahashi;Takayuki Takahashi
S. Rajapakse;Noriko Yamano;K. Ogiwara;K. Hirata;Sumio Takahashi;Takayuki Takahashi
中科院分区:
生物学3区
文献类型:
--
作者:
S. Rajapakse;Noriko Yamano;K. Ogiwara;K. Hirata;Sumio Takahashi;Takayuki Takahashi

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组织激肽激酶mK1是一种丝氨酸蛋白酶,参与小鼠正常心脏和动脉功能的生物活性激肽的产生。在本研究中,组织激肽因子(tissue kallikrein)基因Klk1编码mK1,是成年小鼠子宫中最常见的Klk基因种之一,其mRNA水平在发情期明显高于退情期。经雌二醇- 17β处理的去卵巢小鼠子宫中Klk1 mRNA表达增强。从小鼠分离的子宫内膜上皮细胞和基质细胞在雌二醇- 17β存在下培养时均表现出可检测水平的Klk1表达。利用重组酶对mK1进行了表征。mK1具有胰蛋白酶样活性,在P1位置强烈倾向于精氨酸而不是赖氨酸,其活性被典型的丝氨酸蛋白酶抑制剂抑制。酪蛋白、明胶、纤维连接蛋白、IV型胶原蛋白和高分子量激肽原被mK1降解。单链组织型纤溶酶原激活剂经mK1转化为双链形式。此外,mK1可降解胰岛素样生长因子结合蛋白- 3。目前的数据表明,mK1可能与子宫内膜增生期组织的生长有关。摩尔。天线转换开关。开发。74:1053-1063,2007。©2007 Wiley‐Liss, Inc。
Tissue kallikrein mK1 is a serine protease involved in the generation of bioactive kinins for normal cardiac and arterial function in the mouse. In the present study, the tissue kallikrein gene Klk1, which codes for mK1, was shown to be one of the most prevalent of the Klk gene species in the uteri of adult mice, and its mRNA level was significantly higher at estrus than at diestrus. Klk1 mRNA expression was enhanced in the uteri of ovariectomized mice receiving estradiol‐17β treatment. Both endometrial epithelial and stromal cells isolated from the mice exhibited Klk1 expression at detectable levels when cultured in the presence of estradiol‐17β. mK1 was characterized using the recombinant active enzyme. mK1 had trypsin‐like activity with a strong preference for Arg over Lys in the P1 position, and its activity was inhibited by typical serine protease inhibitors. Casein, gelatin, fibronectin, collagen type IV, and high‐molecular‐weight kininogen were degraded by mK1. The single‐chain tissue‐type plasminogen activator was converted to the two‐chain form by mK1. In addition, mK1 degraded insulin‐like growth factor binding protein‐3. The present data suggest that mK1 may be implicated in the growth of uterine endometrial tissues during the proliferative phase. Mol. Reprod. Dev. 74: 1053–1063, 2007. © 2007 Wiley‐Liss, Inc.