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瘦素及其受体在小鼠乳腺中的表达与功能

Expression and function of leptin and its receptor in mouse mammary gland.

作者信息

Lin Ye, Li QingZhang

机构信息

Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China.

出版信息

Sci China C Life Sci. 2007 Oct;50(5):669-75. doi: 10.1007/s11427-007-0077-2.

DOI:10.1007/s11427-007-0077-2
PMID:17879067
Abstract

Leptin is an autocrine and paracrine factor which affects the development of duct, formation of gland alveolus, expression of milk protein gene and onset involution of mammary gland. In order to know the function and mechanism of leptin in mammary gland, the protein expression and localization of leptin and its long form receptor (OB-Rb) were detected by a confocal laser scanning microscope. To study the impacts of leptin on mammary gland and leptin signal transduction pathway in pregnancy-, lactation-and involution-stage mammary gland, explants were cultured and Western blotting was used. The results showed that in the whole development cycle of mammary gland, the expression of leptin and OB-Rb was in positive correlation. In virgin the leptin expression was the highest and then decreased in pregnancy. In lactation the expression of leptin was low and upgraded in involution, and recovered to the original level about virgin on involution 13 d. The localization of leptin and OB-Rb revealed that leptin induced the expression of OB-Rb specifically and controlled the development and physiological function of the mammary gland by binding to OB-Rb. In pregnancy stage, leptin stimulated proliferation and differentiation of ductal epithelial cells by JAK-MAPK signal pathway. In lactation, leptin induced gene expression of beta-casein by JAK-STAT5 signal pathway, and in involution leptin induced mammary epithelial cell apoptosis and mammary gland restitution by JAK-STAT3 signal pathway.

摘要

瘦素是一种自分泌和旁分泌因子,它影响乳腺导管的发育、腺泡的形成、乳蛋白基因的表达以及乳腺的退化起始。为了了解瘦素在乳腺中的功能和作用机制,利用共聚焦激光扫描显微镜检测了瘦素及其长型受体(OB-Rb)的蛋白表达和定位。为了研究瘦素对妊娠、泌乳和退化期乳腺的影响以及瘦素信号转导通路,进行了外植体培养并使用了蛋白质印迹法。结果表明,在乳腺的整个发育周期中,瘦素和OB-Rb的表达呈正相关。在未孕状态下瘦素表达最高,在妊娠期降低。在泌乳期瘦素表达较低,在退化期升高,并在退化13天时恢复到接近未孕时的水平。瘦素和OB-Rb的定位显示,瘦素特异性诱导OB-Rb的表达,并通过与OB-Rb结合来控制乳腺的发育和生理功能。在妊娠阶段,瘦素通过JAK-MAPK信号通路刺激导管上皮细胞的增殖和分化。在泌乳期,瘦素通过JAK-STAT5信号通路诱导β-酪蛋白的基因表达,在退化期瘦素通过JAK-STAT3信号通路诱导乳腺上皮细胞凋亡和乳腺组织复原。

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