Serveur d'exploration sur la glutarédoxine

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Loss of glutaredoxin 3 impedes mammary lobuloalveolar development during pregnancy and lactation.

Identifieur interne : 000344 ( Main/Exploration ); précédent : 000343; suivant : 000345

Loss of glutaredoxin 3 impedes mammary lobuloalveolar development during pregnancy and lactation.

Auteurs : Khanh Pham [États-Unis] ; Jie Dong [États-Unis] ; Xiqian Jiang [États-Unis] ; Ying Qu [États-Unis] ; Han Yu [États-Unis] ; Yisheng Yang [États-Unis] ; Walter Olea [États-Unis] ; Juan C. Marini [États-Unis] ; Lawrence Chan [États-Unis] ; Jin Wang [États-Unis] ; Xander H T. Wehrens [États-Unis] ; Xiaojiang Cui [États-Unis] ; Yi Li [États-Unis] ; Darryl L. Hadsell [États-Unis] ; Ninghui Cheng [États-Unis]

Source :

RBID : pubmed:27894063

Descripteurs français

English descriptors

Abstract

Mammalian glutaredoxin 3 (Grx3) has been shown to be important for regulating cellular redox homeostasis in the cell. Our previous studies indicate that Grx3 is significantly overexpressed in various human cancers including breast cancer and demonstrate that Grx3 controls cancer cell growth and invasion by regulating reactive oxygen species (ROS) and NF-κB signaling pathways. However, it remains to be determined whether Grx3 is required for normal mammary gland development and how it contributes to epithelial cell proliferation and differentiation in vivo. In the present study, we examined Grx3 expression in different cell types within the developing mouse mammary gland (MG) and found enhanced expression of Grx3 at pregnancy and lactation stages. To assess the physiological role of Grx3 in MG, we generated the mutant mice in which Grx3 was deleted specifically in mammary epithelial cells (MECs). Although the reduction of Grx3 expression had only minimal effects on mammary ductal development in virgin mice, it did reduce alveolar density during pregnancy and lactation. The impairment of lobuloalveolar development was associated with high levels of ROS accumulation and reduced expression of milk protein genes. In addition, proliferative gene expression was significantly suppressed with proliferation defects occurring in knockout MECs during alveolar development compared with wild-type controls. Therefore, our findings suggest that Grx3 is a key regulator of ROS in vivo and is involved in pregnancy-dependent mammary gland development and secretory activation through modulating cellular ROS.

DOI: 10.1152/ajpendo.00150.2016
PubMed: 27894063
PubMed Central: PMC5374299


Affiliations:


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Le document en format XML

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<name sortKey="Dong, Jie" sort="Dong, Jie" uniqKey="Dong J" first="Jie" last="Dong">Jie Dong</name>
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<name sortKey="Cui, Xiaojiang" sort="Cui, Xiaojiang" uniqKey="Cui X" first="Xiaojiang" last="Cui">Xiaojiang Cui</name>
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<name sortKey="Li, Yi" sort="Li, Yi" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name>
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<nlm:affiliation>Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.</nlm:affiliation>
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<name sortKey="Hadsell, Darryl L" sort="Hadsell, Darryl L" uniqKey="Hadsell D" first="Darryl L" last="Hadsell">Darryl L. Hadsell</name>
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<region type="state">Texas</region>
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<wicri:cityArea>Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston</wicri:cityArea>
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<name sortKey="Cheng, Ninghui" sort="Cheng, Ninghui" uniqKey="Cheng N" first="Ninghui" last="Cheng">Ninghui Cheng</name>
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<affiliation>
<nlm:affiliation>Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas; and.</nlm:affiliation>
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<title level="j">American journal of physiology. Endocrinology and metabolism</title>
<idno type="eISSN">1522-1555</idno>
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<term>Animals (MeSH)</term>
<term>Blotting, Western (MeSH)</term>
<term>Cell Proliferation (genetics)</term>
<term>Cyclin D1 (genetics)</term>
<term>Epithelial Cells (metabolism)</term>
<term>Female (MeSH)</term>
<term>Gene Expression Regulation, Developmental (MeSH)</term>
<term>Glutaredoxins (genetics)</term>
<term>Immunohistochemistry (MeSH)</term>
<term>Lactation (genetics)</term>
<term>Mammary Glands, Animal (growth & development)</term>
<term>Mammary Glands, Animal (metabolism)</term>
<term>Mice (MeSH)</term>
<term>Mice, Knockout (MeSH)</term>
<term>Milk Proteins (genetics)</term>
<term>NF-kappa B (metabolism)</term>
<term>Pregnancy (MeSH)</term>
<term>Pregnancy, Animal (MeSH)</term>
<term>RANK Ligand (metabolism)</term>
<term>RNA, Messenger (metabolism)</term>
<term>Reactive Oxygen Species (metabolism)</term>
<term>Real-Time Polymerase Chain Reaction (MeSH)</term>
<term>Receptor Activator of Nuclear Factor-kappa B (metabolism)</term>
<term>Receptors, Progesterone (metabolism)</term>
<term>Signal Transduction (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>ARN messager (métabolisme)</term>
<term>Animaux (MeSH)</term>
<term>Cellules épithéliales (métabolisme)</term>
<term>Cycline D1 (génétique)</term>
<term>Espèces réactives de l'oxygène (métabolisme)</term>
<term>Facteur de transcription NF-kappa B (métabolisme)</term>
<term>Femelle (MeSH)</term>
<term>Gestation animale (MeSH)</term>
<term>Glandes mammaires animales (croissance et développement)</term>
<term>Glandes mammaires animales (métabolisme)</term>
<term>Glutarédoxines (génétique)</term>
<term>Grossesse (MeSH)</term>
<term>Immunohistochimie (MeSH)</term>
<term>Lactation (génétique)</term>
<term>Ligand de RANK (métabolisme)</term>
<term>Prolifération cellulaire (génétique)</term>
<term>Protéines de lait (génétique)</term>
<term>Réaction de polymérisation en chaine en temps réel (MeSH)</term>
<term>Récepteur activateur du facteur nucléaire Kappa B (métabolisme)</term>
<term>Récepteurs à la progestérone (métabolisme)</term>
<term>Régulation de l'expression des gènes au cours du développement (MeSH)</term>
<term>Souris (MeSH)</term>
<term>Souris knockout (MeSH)</term>
<term>Technique de Western (MeSH)</term>
<term>Transduction du signal (MeSH)</term>
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<term>Cyclin D1</term>
<term>Glutaredoxins</term>
<term>Milk Proteins</term>
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<term>Glandes mammaires animales</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Cell Proliferation</term>
<term>Lactation</term>
</keywords>
<keywords scheme="MESH" qualifier="growth & development" xml:lang="en">
<term>Mammary Glands, Animal</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Cycline D1</term>
<term>Glutarédoxines</term>
<term>Lactation</term>
<term>Prolifération cellulaire</term>
<term>Protéines de lait</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Epithelial Cells</term>
<term>Mammary Glands, Animal</term>
<term>NF-kappa B</term>
<term>RANK Ligand</term>
<term>RNA, Messenger</term>
<term>Reactive Oxygen Species</term>
<term>Receptor Activator of Nuclear Factor-kappa B</term>
<term>Receptors, Progesterone</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>ARN messager</term>
<term>Cellules épithéliales</term>
<term>Espèces réactives de l'oxygène</term>
<term>Facteur de transcription NF-kappa B</term>
<term>Glandes mammaires animales</term>
<term>Ligand de RANK</term>
<term>Récepteur activateur du facteur nucléaire Kappa B</term>
<term>Récepteurs à la progestérone</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Blotting, Western</term>
<term>Female</term>
<term>Gene Expression Regulation, Developmental</term>
<term>Immunohistochemistry</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Pregnancy</term>
<term>Pregnancy, Animal</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Femelle</term>
<term>Gestation animale</term>
<term>Grossesse</term>
<term>Immunohistochimie</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Régulation de l'expression des gènes au cours du développement</term>
<term>Souris</term>
<term>Souris knockout</term>
<term>Technique de Western</term>
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<front>
<div type="abstract" xml:lang="en">Mammalian glutaredoxin 3 (Grx3) has been shown to be important for regulating cellular redox homeostasis in the cell. Our previous studies indicate that Grx3 is significantly overexpressed in various human cancers including breast cancer and demonstrate that Grx3 controls cancer cell growth and invasion by regulating reactive oxygen species (ROS) and NF-κB signaling pathways. However, it remains to be determined whether Grx3 is required for normal mammary gland development and how it contributes to epithelial cell proliferation and differentiation in vivo. In the present study, we examined Grx3 expression in different cell types within the developing mouse mammary gland (MG) and found enhanced expression of
<i>Grx3</i>
at pregnancy and lactation stages. To assess the physiological role of Grx3 in MG, we generated the mutant mice in which
<i>Grx3</i>
was deleted specifically in mammary epithelial cells (MECs). Although the reduction of
<i>Grx3</i>
expression had only minimal effects on mammary ductal development in virgin mice, it did reduce alveolar density during pregnancy and lactation. The impairment of lobuloalveolar development was associated with high levels of ROS accumulation and reduced expression of milk protein genes. In addition, proliferative gene expression was significantly suppressed with proliferation defects occurring in knockout MECs during alveolar development compared with wild-type controls. Therefore, our findings suggest that Grx3 is a key regulator of ROS in vivo and is involved in pregnancy-dependent mammary gland development and secretory activation through modulating cellular ROS.</div>
</front>
</TEI>
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<DateCompleted>
<Year>2017</Year>
<Month>06</Month>
<Day>26</Day>
</DateCompleted>
<DateRevised>
<Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1522-1555</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>312</Volume>
<Issue>3</Issue>
<PubDate>
<Year>2017</Year>
<Month>03</Month>
<Day>01</Day>
</PubDate>
</JournalIssue>
<Title>American journal of physiology. Endocrinology and metabolism</Title>
<ISOAbbreviation>Am J Physiol Endocrinol Metab</ISOAbbreviation>
</Journal>
<ArticleTitle>Loss of glutaredoxin 3 impedes mammary lobuloalveolar development during pregnancy and lactation.</ArticleTitle>
<Pagination>
<MedlinePgn>E136-E149</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1152/ajpendo.00150.2016</ELocationID>
<Abstract>
<AbstractText>Mammalian glutaredoxin 3 (Grx3) has been shown to be important for regulating cellular redox homeostasis in the cell. Our previous studies indicate that Grx3 is significantly overexpressed in various human cancers including breast cancer and demonstrate that Grx3 controls cancer cell growth and invasion by regulating reactive oxygen species (ROS) and NF-κB signaling pathways. However, it remains to be determined whether Grx3 is required for normal mammary gland development and how it contributes to epithelial cell proliferation and differentiation in vivo. In the present study, we examined Grx3 expression in different cell types within the developing mouse mammary gland (MG) and found enhanced expression of
<i>Grx3</i>
at pregnancy and lactation stages. To assess the physiological role of Grx3 in MG, we generated the mutant mice in which
<i>Grx3</i>
was deleted specifically in mammary epithelial cells (MECs). Although the reduction of
<i>Grx3</i>
expression had only minimal effects on mammary ductal development in virgin mice, it did reduce alveolar density during pregnancy and lactation. The impairment of lobuloalveolar development was associated with high levels of ROS accumulation and reduced expression of milk protein genes. In addition, proliferative gene expression was significantly suppressed with proliferation defects occurring in knockout MECs during alveolar development compared with wild-type controls. Therefore, our findings suggest that Grx3 is a key regulator of ROS in vivo and is involved in pregnancy-dependent mammary gland development and secretory activation through modulating cellular ROS.</AbstractText>
</Abstract>
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</AffiliationInfo>
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<ForeName>Han</ForeName>
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<ForeName>Yisheng</ForeName>
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</AffiliationInfo>
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<ForeName>Walter</ForeName>
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<AffiliationInfo>
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<AffiliationInfo>
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<AffiliationInfo>
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<AffiliationInfo>
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<MeshHeading>
<DescriptorName UI="D008894" MajorTopicYN="N">Milk Proteins</DescriptorName>
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<Keyword MajorTopicYN="Y">alveologenesis</Keyword>
<Keyword MajorTopicYN="Y">breast cancer</Keyword>
<Keyword MajorTopicYN="Y">glutaredoxin</Keyword>
<Keyword MajorTopicYN="Y">mammary epithelial cells</Keyword>
<Keyword MajorTopicYN="Y">mammary gland</Keyword>
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<Year>2016</Year>
<Month>04</Month>
<Day>15</Day>
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<PubMedPubDate PubStatus="revised">
<Year>2016</Year>
<Month>10</Month>
<Day>26</Day>
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<Month>11</Month>
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