scholarly journals Mammary mechanobiology: mechanically-activated ion channels in lactation and involution

2019 ◽  
Author(s):  
Teneale A. Stewart ◽  
Katherine Hughes ◽  
Alexander J. Stevenson ◽  
Natascia Marino ◽  
Adler L. Ju ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Food Source ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Mechanical Forces ◽  
Offspring Survival ◽  
Evolutionary Advantage ◽  
And Function ◽  
Mechanical Sensing

AbstractA mother’s ability to produce a nutritionally-complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by secretory mammary epithelial cells is adaptive, its release is exquisitely timed and its own glandular stagnation with the permanent cessation of suckling triggers the programmed cell death and tissue remodeling that enables female mammals to nurse successive progeny. Both chemical and mechanical signals control epithelial expansion, function and remodeling. Despite this duality of input, however, the nature and function of mechanical forces in the mammary gland remain unknown. Here, we characterize the mammary force landscape and the capacity of luminal and basal epithelial cells to experience and exert force. We explore the molecular instruments for force-sensing in the mammary gland and the physiological requirement for PIEZO1 in lactation and involution. Our study supports the existence of a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.

scholarly journals Mammary mechanobiology – investigating roles for mechanically activated ion channels in lactation and involution

2020 ◽  
Vol 134 (1) ◽  
pp. jcs248849 ◽  
Author(s):  
Teneale A. Stewart ◽  
Katherine Hughes ◽  
Alexander J. Stevenson ◽  
Natascia Marino ◽  
Adler L. Ju ◽  
...  
Keyword(s):  
Mammary Epithelial Cells ◽  
Functional Expression ◽  
Mammary Epithelial ◽  
Mammary Tissue ◽  
Basal Cells ◽  
Offspring Survival ◽  
Evolutionary Advantage ◽  
Luminal Cells ◽  
And Function ◽  
Mechanical Sensing

ABSTRACTThe ability of a mother to produce a nutritionally complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by mammary epithelial cells is adaptive, its release is exquisitely timed, and its own glandular stagnation with the permanent cessation of suckling triggers the cell death and tissue remodeling that enables female mammals to nurse successive progeny. Chemical and mechanical signals both play a role in this process. However, despite this duality of input, much remains unknown about the nature and function of mechanical forces in this organ. Here, we characterize the force landscape in the functionally mature gland and the capacity of luminal and basal cells to experience and exert force. We explore molecular instruments for force-sensing, in particular channel-mediated mechanotransduction, revealing increased expression of Piezo1 in mammary tissue in lactation and confirming functional expression in luminal cells. We also reveal, however, that lactation and involution proceed normally in mice with luminal-specific Piezo1 deletion. These findings support a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.

scholarly journals Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47876 ◽  
Author(s):  
Sonia M. Rosenfield ◽  
Emma T. Bowden ◽  
Shani Cohen-Missner ◽  
Krissa A. Gibby ◽  
Virginie Ory ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
And Function

scholarly journals The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Vaibhav P. Pai ◽  
Laura L. Hernandez ◽  
Malinda A. Stull ◽  
Nelson D. Horseman
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Serotonin Receptor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelium ◽  
Mammary Epithelial ◽  
Lactation Performance ◽  
Epithelial Structure ◽  
And Function ◽  
First Time

Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer.

scholarly journals Targeted Expression of GLI1 in the Mammary Gland Disrupts Pregnancy-induced Maturation and Causes Lactation Failure

2007 ◽  
Vol 282 (49) ◽  
pp. 36090-36101 ◽  
Author(s):  
Marie Fiaschi ◽  
Björn Rozell ◽  
Åsa Bergström ◽  
Rune Toftgård ◽  
Marika I. Kleman
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Hedgehog Signaling Pathway ◽  
Milk Protein Gene ◽  
Milk Protein Gene Expression ◽  
And Function

The Hedgehog signaling pathway regulates the development and function of numerous tissues and when mis-regulated causes tumorigenesis. To assess the role of a deregulated Hedgehog signaling pathway in the mammary gland we targeted the expression of the Hedgehog effector protein, GLI1, to mammary epithelial cells using a bigenic inducible system. A constitutively active Hedgehog signaling pathway resulted with 100% penetrance in an undifferentiated mammary lobuloalveolar network during pregnancy. GLI1-expressing transgenic females were unable to lactate and milk protein gene expression was essentially absent. The inability to lactate was permanent and independent of continued GLI1 transgene expression. An increased expression of the GLI1 response gene Snail coupled to reduced expression of E-cadherin and STAT5 in the transgenic mammary gland provides a likely molecular explanation, underlying the observed phenotypic changes. In addition, remodeling of the mammary gland after parturition was impaired and expression of GLI1 was associated with accumulation of cellular debris in the mammary ducts during involution, indicating a defect in the clearance of dead cells. Areas with highly proliferative epithelial cells were observed in mammary glands with induced expression of GLI1. Within such areas an increased frequency of cells expressing nuclear Cyclin D1 was observed. Taken together the data support the notion that correct regulation of Hedgehog signaling within the epithelial cell compartment is critical for pregnancy-induced mammary gland development and remodeling.

scholarly journals Correction: Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
Author(s):  
Sonia M. Rosenfield ◽  
Emma T. Bowden ◽  
Shani Cohen-Missner ◽  
Krissa A. Gibby ◽  
Virginie Ory ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
And Function

scholarly journals Laminin alpha 5 is Necessary for Mammary Epithelial Growth and Function by Maintaining Luminal Epithelial Cell Identity

2019 ◽  
Author(s):  
Johanna I Englund ◽  
Hanne Cojoc ◽  
Leander Blaas ◽  
Alexandra Ritchie ◽  
Nalle Pentinmikko ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Normal Mammary Gland ◽  
Hormone Receptor Positive ◽  
And Function ◽  
Gland Development ◽  
Luminal Epithelial Cells ◽  
Basal Epithelial Cells

ABSTRACTEpithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we demonstrate that expression of distinct laminin α-isoforms by luminal and basal mammary epithelial cells enforces lineage identity that is necessary for normal mammary gland growth and function. Laminin α5 (LMα5) is mainly expressed by the luminal epithelial cells, and it is necessary for pubertal mammary gland growth, pregnancy induced gland remodeling, and for alveolar function. Adhesion to LMα5 containing laminin promotes luminal traits in both luminal and basal epithelial cells, and reduces progenitor activity of basal epithelial cells. Mechanistically, we show that Lama5 loss interferes with differentiation of hormone receptor positive luminal cells, which results in reduced Wnt4 expression and defective crosstalk between luminal and basal epithelial cells during gland remodeling. Our results reveal a novel BM-mediated mechanism, which regulates mammary gland remodeling and function via specification of luminal epithelial cells.

scholarly journals Evidence of Rab3A Expression, Regulation of Vesicle Trafficking, and Cellular Secretion in Response to Heregulin in Mammary Epithelial Cells

2000 ◽  
Vol 20 (23) ◽  
pp. 9092-9101 ◽  
Author(s):  
Ratna K. Vadlamudi ◽  
Rui-An Wang ◽  
Amjad H. Talukder ◽  
Liana Adam ◽  
Randy Johnson ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Vesicle Trafficking ◽  
Mammary Epithelial ◽  
Coated Vesicle ◽  
Human Breast ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Stimulation Of

ABSTRACT Heregulin β1 (HRG), a combinatorial ligand for human growth factor receptors 3 and 4, is a regulatory polypeptide that promotes the differentiation of mammary epithelial cells into secretory lobuloalveoli. Emerging evidence suggests that the processes of secretory pathways, such as biogenesis and trafficking of vesicles in neurons and adipose cells, are regulated by the Rab family of low-molecular-weight GTPases. In this study, we identified Rab3A as a gene product induced by HRG. Full-length Rab3A was cloned from a mammary gland cDNA library. We demonstrated that HRG stimulation of human breast cancer cells and normal breast epithelial cells induces the expression of Rab3A protein and mRNA in a cycloheximide-independent manner. HRG-mediated induction of Rab3A expression was blocked by an inhibitor of phosphatidylinositol 3-kinase but not by inhibitors of mitogen-activated protein kinases p38MAPK and p42/44MAPK. Human breast epithelial cells also express other components of regulated vesicular traffic, such as rabphilin 3A, Doc2, and syntaxin. Rab3A was predominantly localized in the cytosol, and HRG stimulation of the epithelial cells also raised the level of membrane-bound Rab3A. HRG treatment induced a profound alteration in the cell morphology in which cells displayed neuron-like membrane extensions that contained Rab3A-coated, vesicle-like structures. In addition, HRG also promoted the secretion of cellular proteins from the mammary epithelial cells. The ability of HRG to modify exocytosis was verified by using a growth hormone transient-transfection system. Analysis of mouse mammary gland development revealed the expression of Rab3A in mammary epithelial cells. Furthermore, expression of the HRG transgene in Harderian tumors in mice also enhanced the expression of Rab3A. These observations provide new evidence of the existence of a Rab3A pathway in mammary epithelial cells and suggest that it may play a role in vesicle trafficking and secretion of proteins from epithelial cells in response to stimulation by the HRG expressed within the mammary mesenchyma.

MicroRNA-432 inhibits milk fat synthesis by targeting SCD and LPL in ovine mammary epithelial cells

2021 ◽  
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jon Hickford ◽  
Huitong Zhou ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Milk Production ◽  
Milk Fat ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Fat Synthesis ◽  
Milk Fat Synthesis

In our previous studies, microRNA-432 (miR-432) was found to be one of differentially expressed miRNAs in ovine mammary gland between the two breeds of lactating sheep with different milk production...

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