Altered expression of tight junction proteins in mammary epithelium after discontinued suckling in mice

Altered expression of tight junction proteins in mammary epithelium after discontinued suckling in mice
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小鼠停止哺乳后乳腺上皮中紧密连接蛋白表达的改变

DOI:
10.1007/s00424-011-1034-2
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发表时间:
2012
期刊:
Pflügers Archiv - European Journal of Physiology
影响因子:
--
通讯作者:
Amasheh S
Amasheh S
中科院分区:
--
文献类型:
--
作者:
Markov AG;Kruglova NM;Fomina YA;Fromm M;Amasheh S

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乳汁的产生是由位于乳腺上皮中的紧密连接(TJ)蛋白的细胞旁屏障功能调节的。我们的研究的目的是在自然哺乳期小鼠乳腺上皮细胞的TJ的分子分析,因为这一过程可能会强烈挑战上皮屏障特性和调节。哺乳对照组小鼠和哺乳中断20 h后动物的乳腺组织标本制备;通过光镜和电镜进行组织学分析;通过PCR、Western印迹、免疫荧光染色和共聚焦激光扫描显微镜检测TJ蛋白的表达。停止哺乳导致乳汁在乳腺中大量积聚,肺泡大小增加,上皮细胞变平,对炎症指标无影响。在对照组织中,PCR和蛋白质印迹显示闭合蛋白和封闭蛋白-1、-2、-3、-4、-5、-7、-8、-15和-16的信号。经过20小时的牛奶积累,密封TJ蛋白,claudin-1和-3,表达显着增加,而两个TJ蛋白参与阳离子转运,claudin-2和-16,减少。实时PCR验证了claudin-1和claudin-3的转录增加。在泌乳过程中乳腺的伸展过程中,claudin-1和claudin-3被显著诱导,claudin-2和claudin-16被降低。乳汁的体积和组成可能强烈依赖于密封密封蛋白与渗透性介导的密封蛋白的这种反调节,这表明TJ收紧以防止溶质和离子从肺泡腔回漏的生理过程。
Milk production is modulated by the paracellular barrier function of tight junction (TJ) proteins located in the mammary epithelium. The aim of our study was the molecular analysis of TJs in native lactating murine mammary gland epithelium as this process may strongly challenge epithelial barrier properties and regulation. Mammary gland tissue specimens from lactating control mice and animals after a 20-h interruption of suckling were prepared; histological analyses were performed by light and electron microscopy; and expression of TJ proteins was detected by PCR, Western blotting, immunofluorescent staining, and confocal laser scanning microscopy. Discontinuation of suckling resulted in a substantial accumulation of milk in mammary glands, an increase of alveolar size, and a flattening of epithelial cells without effects on inflammatory indicators. In control tissues, PCR and Western blots showed signals for occludin, and claudin-1, -2, -3, -4, -5, -7, -8, -15, and -16. After a 20-h accumulation of milk, expression of two sealing TJ proteins, claudin-1 and -3, was markedly increased, whereas two TJ proteins involved in cation transport, claudin-2 and -16, were reduced. Real-time PCR validated increased transcripts of claudin-1 and claudin-3. During extension of mammary glands in the process of lactation, claudin-1 and -3 are markedly induced and claudin-2 and -16 are decreased. Volume and composition of milk might be strongly dependent on this counter-regulation of sealing claudins with permeability-mediating claudins, indicating a physiological process of a tightening of TJs against a back-leak of solutes and ions from the alveolar lumen.
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发表时间: 2008-11
期刊: Gut
影响因子: 24.5
作者:
H. Troeger;C. Loddenkemper;T. Schneider;E. Schreier;H. Epple;M. Zeitz;M. Fromm;J. Schulzke
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发表时间: 2010-11-01
影响因子: 3.4
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DOI: 10.1172/jci26323
发表时间: 2006-04-01
影响因子: 15.9
作者:
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通讯作者: Hunziker, W
DOI: 10.1016/j.bbrc.2004.03.072
发表时间: 2004-04-30
影响因子: 3.1
作者:
Barmeyer, C;Amasheh, S;Schulzke, JD
通讯作者: Schulzke, JD