Increased gene expression of endothelin-1 and vasoactive intestinal contractor/endothelin-2 in the mammary gland of lactating mice

Kozakai, Takaharu; Sakate, Mitsue; Masuo, Yoshinori; Uchide, Tsuyoshi; Saida, Kaname

doi:10.1016/s0006-291x(02)02224-6

Cited by 8 publications

(3 citation statements)

References 28 publications

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“…The most upregulated gene in mPINC knockdown cells, Edn1 , is an important cell fate determinant during embryogenesis [58], [59]. It is highly expressed in the mammary gland during lactation and is also induced in HC11 cells treated with lactogenic hormones [60]. The receptor for Edn1 , Ednra , was downregulated by mPINC modulation, thus emphasizing the potential importance of this pathway.…”

Section: Discussionmentioning

confidence: 97%

Pregnancy-Induced Noncoding RNA (PINC) Associates with Polycomb Repressive Complex 2 and Regulates Mammary Epithelial Differentiation

et al. 2012

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Pregnancy-induced noncoding RNA (PINC) and retinoblastoma-associated protein 46 (RbAp46) are upregulated in alveolar cells of the mammary gland during pregnancy and persist in alveolar cells that remain in the regressed lobules following involution. The cells that survive involution are thought to function as alveolar progenitor cells that rapidly differentiate into milk-producing cells in subsequent pregnancies, but it is unknown whether PINC and RbAp46 are involved in maintaining this progenitor population. Here, we show that, in the post-pubertal mouse mammary gland, mPINC is enriched in luminal and alveolar progenitors. mPINC levels increase throughout pregnancy and then decline in early lactation, when alveolar cells undergo terminal differentiation. Accordingly, mPINC expression is significantly decreased when HC11 mammary epithelial cells are induced to differentiate and produce milk proteins. This reduction in mPINC levels may be necessary for lactation, as overexpression of mPINC in HC11 cells blocks lactogenic differentiation, while knockdown of mPINC enhances differentiation. Finally, we demonstrate that mPINC interacts with RbAp46, as well as other members of the polycomb repressive complex 2 (PRC2), and identify potential targets of mPINC that are differentially expressed following modulation of mPINC expression levels. Taken together, our data suggest that mPINC inhibits terminal differentiation of alveolar cells during pregnancy to prevent abundant milk production and secretion until parturition. Additionally, a PRC2 complex that includes mPINC and RbAp46 may confer epigenetic modifications that maintain a population of mammary epithelial cells committed to the alveolar fate in the involuted gland.

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Section: Discussionmentioning

confidence: 97%

Pregnancy-Induced Noncoding RNA (PINC) Associates with Polycomb Repressive Complex 2 and Regulates Mammary Epithelial Differentiation

et al. 2012

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“…The method used has been described previously [35]. Sample cDNA for real-time PCR was obtained by reverse transcriptase reaction of total RNA.…”

Section: Real-time Polymerase Chain Reaction (Pcr) For Et-1mentioning

confidence: 99%

Regulation of endothelin-1 expression and function by nutrient stress in mouse colon epithelia

Kozakai

Sakate

Saida

2008

Scandinavian Journal of Gastroenterology

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“…Özellikle sütte ET-1'in varlığı, pek çok peptid ve büyüme faktörü gibi, hem emziren anne hem de yeni doğanın fizyolojisinde önemli bir rolü olduğunu düşündürmektedir (10). Ayrıca meme bezi gelişiminde ve fizyolojisinde anahtar hormonlardan biri olan prolaktin hormonunun ET-1'in ifadesini güçlü bir şekilde indüklediği (11) tespit edilmiş ve ET-1'in gen ifadesinin özellikle gebelik sırasında başlayıp laktasyon dönemi boyunca devam ettiği önceki çalışmalarda belirtilmiştir (12). Bu bağlamda, ET-1'in meme bezi gelişimi üzerine etkisi ve olası fonksiyonel rollerini aydınlatmak üzere ET-1 transgenik fareler kullanarak bu çalışma tasarlanmıştır.…”

Section: Introductionunclassified

Yüksek ET-1 İfadesinin Meme Bezi Fizyolojisi Üzerine Etkileri

Gül¹,

Theuring²

2021

experimed

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Objective: Alongside its role as a potent vasoconstrictor in the cardiovascular system, endothelin-1 (ET-1) is involved in numerous physiological processes. Its expression is thought to be an important function for both breastfeeding and newborns since it occurs especially during pregnancy and lactation. In this study, we projected the effects of ET-1 on mammary gland physiology employing ET-1 transgenic mice. Materials and Methods:In this study, we compared the mammary glands of ET-1 transgenic mice with the control mice in different physiological states (adolescence, pregnant, lactation and involution). Parallel sections were prepared from mammary glands and microscopic examinations were performed with hematoxylin and eosin (HE)-staining. Western blot techniques were used in the analysis of signal proteins that have important functions in mammary gland development and the metabolism (STAT5, AKT, STAT3). Genes known to play a key function in metabolic activities (WAP, beta casein, GLUT-1, SRBF-1 Claudin 8, IL-6, LIF) were analyzed employing real-time PCR techniques.Results: It was determined that ET-1 transgenic mice developed pathological conditions such as secretory damage, lactational failure and early involution, respectively. Our western blot studies showed that STAT5 activation was not affected by this process in the transgenic group, but a decrease in AKT protein level was detected. We detected STAT3 activation seen in the involution process in transgenic mice only on the 3rd day of lactation. In addition, we found that WAP was suppressed due to high ET-1 expression and that LIF protein expression increased significantly, by real-time PCR analysis. Conclusion:ET-1 expression is thought to be an important function for both lactation and newborns, especially during pregnancy and lactation. In this study, it was found that when ET-1 expression increases, it causes lactation failure in the mammary gland and directly affects the synthesis of genes known to be important in mammary physiology. Hereby, it was determined that the regulation of ET-1 plays a critical role in the development and secretory function of the mammary gland.

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Increased gene expression of endothelin-1 and vasoactive intestinal contractor/endothelin-2 in the mammary gland of lactating mice

Cited by 8 publications

References 28 publications

Pregnancy-Induced Noncoding RNA (PINC) Associates with Polycomb Repressive Complex 2 and Regulates Mammary Epithelial Differentiation

Pregnancy-Induced Noncoding RNA (PINC) Associates with Polycomb Repressive Complex 2 and Regulates Mammary Epithelial Differentiation

Regulation of endothelin-1 expression and function by nutrient stress in mouse colon epithelia

Yüksek ET-1 İfadesinin Meme Bezi Fizyolojisi Üzerine Etkileri

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