Telocytes are associated with tissue remodeling and angiogenesis during the postlactational involution of the mammary gland in gerbils

2020 ◽  
Vol 44 (12) ◽  
pp. 2512-2523
Author(s):  
Bruno D. A. Sanches ◽  
Ellen C. R. Leonel ◽  
Juliana S. Maldarine ◽  
Guilherme H. Tamarindo ◽  
Caroline N. Barquilha ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Tissue Remodeling ◽  
Postlactational Involution

scholarly journals ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution

2018 ◽  
Vol 315 (2) ◽  
pp. R323-R335 ◽  
Author(s):  
Olivia C. Rivera ◽  
Stephen R. Hennigar ◽  
Shannon L. Kelleher
Keyword(s):  
Cell Death ◽  
Mammary Gland ◽  
Mammary Epithelial Cells ◽  
Tissue Remodeling ◽  
Vacuolar Atpase ◽  
Mammary Epithelial ◽  
Direct Role ◽  
Lysosome Biogenesis ◽  
Mammary Gland Involution ◽  
Lactating Mammary Gland

Mammary gland involution, a tightly regulated process of tissue remodeling by which a lactating mammary gland reverts to the prepregnant state, is characterized by the most profound example of regulated epithelial cell death in normal tissue. Defects in the execution of involution are associated with lactation failure and breast cancer. Initiation of mammary gland involution requires upregulation of lysosome biogenesis and acidification to activate lysosome-mediated cell death; however, specific mediators of this initial phase of involution are not well described. Zinc transporter 2 [ZnT2 ( SLC30A2)] has been implicated in lysosome biogenesis and lysosome-mediated cell death during involution; however, the direct role of ZnT2 in this process has not been elucidated. Here we showed that ZnT2-null mice had impaired alveolar regression and reduced activation of the involution marker phosphorylated Stat3, indicating insufficient initiation of mammary gland remodeling during involution. Moreover, we found that the loss of ZnT2 inhibited assembly of the proton transporter vacuolar ATPase on lysosomes, thereby decreasing lysosome abundance and size. Studies in cultured mammary epithelial cells revealed that while the involution signal TNFα promoted lysosome biogenesis and acidification, attenuation of ZnT2 impaired the lysosome response to this involution signal, which was not a consequence of cytoplasmic Zn accumulation. Our findings establish ZnT2 as a novel regulator of vacuolar ATPase assembly, driving lysosome biogenesis, acidification, and tissue remodeling during the initiation of mammary gland involution.

scholarly journals A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

Oncogene ◽  
2015 ◽  
Vol 34 (36) ◽  
pp. 4777-4790 ◽  
Author(s):  
S Castillo-Lluva ◽  
L Hontecillas-Prieto ◽  
A Blanco-Gómez ◽  
M del Mar Sáez-Freire ◽  
B García-Cenador ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Cancer Development ◽  
Luminal Breast Cancer ◽  
Breast Cancer Development ◽  
Postlactational Involution

scholarly journals Bin1 Ablation in Mammary Gland Delays Tissue Remodeling and Drives Cancer Progression

2007 ◽  
Vol 67 (1) ◽  
pp. 100-107 ◽  
Author(s):  
Mee Young Chang ◽  
Janette Boulden ◽  
Erika Sutanto-Ward ◽  
James B. Duhadaway ◽  
Alejandro Peralta Soler ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Cancer Progression ◽  
Tissue Remodeling

scholarly journals Erratum: A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

Oncogene ◽  
2015 ◽  
Vol 34 (36) ◽  
pp. 4797-4798 ◽  
Author(s):  
S Castillo-Lluva ◽  
L Hontecillas-Prieto ◽  
A Blanco-Gómez ◽  
M del Mar Sáez-Freire ◽  
B García-Cenador ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Cancer Development ◽  
Luminal Breast Cancer ◽  
Breast Cancer Development ◽  
Postlactational Involution

scholarly journals Alterations in mast cell frequency and relationship to angiogenesis in the rat mammary gland during windows of physiologic tissue remodeling

2012 ◽  
Vol 241 (5) ◽  
pp. 890-900 ◽  
Author(s):  
Robert A. Ramirez ◽  
Amy Lee ◽  
Pepper Schedin ◽  
Joshua S. Russell ◽  
Patricia A. Masso-Welch
Keyword(s):  
Mast Cell ◽  
Mammary Gland ◽  
Tissue Remodeling ◽  
Cell Frequency ◽  
Rat Mammary Gland

scholarly journals Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 181-193 ◽  
Author(s):  
L.R. Lund ◽  
J. Romer ◽  
N. Thomasset ◽  
H. Solberg ◽  
C. Pyke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Tissue Remodeling ◽  
Apoptotic Cells ◽  
Gelatinase A ◽  
Casein Gene ◽  
Mammary Gland Involution ◽  
Beta Casein

Postlactational involution of the mammary gland is characterized by two distinct physiological events: apoptosis of the secretory, epithelial cells undergoing programmed cell death, and proteolytic degradation of the mammary gland basement membrane. We examined the spatial and temporal patterns of apoptotic cells in relation to those of proteinases during involution of the BALB/c mouse mammary gland. Apoptosis was almost absent during lactation but became evident at day 2 of involution, when beta-casein gene expression was still high. Apoptotic cells were then seen at least up to day 8 of involution, when beta-casein gene expression was being extinguished. Expression of sulfated glycoprotein-2 (SGP-2), interleukin-1 beta converting enzyme (ICE) and tissue inhibitor of metalloproteinases-1 was upregulated at day 2, when apoptotic cells were seen initially. Expression of the matrix metalloproteinases gelatinase A and stromelysin-1 and the serine proteinase urokinase-type plasminogen activator, which was low during lactation, was strongly upregulated in parallel starting at day 4 after weaning, coinciding with start of the collapse of the lobulo-alveolar structures and the intensive tissue remodeling in involution. The major sites of mRNA synthesis for these proteinases were fibroblast-like cells in the periductal stroma and stromal cells surrounding the collapsed alveoli, suggesting that the degradative phase of involution is due to a specialized mesenchymal-epithelial interaction. To elucidate the functional role of these proteinases during involution, at the onset of weaning we treated mice systemically with the glucocorticoid hydrocortisone, which is known to inhibit mammary gland involution. Although the initial wave of apoptotic cells appeared in the lumina of the gland, the dramatic regression and tissue remodeling usually evident by day 5 was substantially inhibited by systemic treatment with hydrocortisone. mRNA and protein for gelatinase A, stromelysin-1 and uPA were weakly induced, if at all, in hydrocortisone-treated mice. Furthermore, mRNA for membrane-type matrix metalloproteinase decreased after hydrocortisone treatment and paralleled the almost complete inhibition of activation of latent gelatinase A. Concomitantly, the gland filled with an overabundance of milk. Our data support the hypothesis that there are at least two distinct phases of involution: an initial phase, characterized by induction of the apoptosis-associated genes SGP-2 and ICE and apoptosis of fully differentiated mammary epithelial cells without visible degradation of the extracellular matrix, and a second phase, characterized by extracellular matrix remodeling and altered mesenchymal-epithelial interactions, followed by apoptosis of cells that are losing differentiated functions.

scholarly journals Accelerated Mammary Gland Development during Pregnancy and Delayed Postlactational Involution in Vitamin D3 Receptor Null Mice

2004 ◽  
Vol 18 (9) ◽  
pp. 2208-2223 ◽  
Author(s):  
Glendon M. Zinser ◽  
JoEllen Welsh
Keyword(s):  
Vitamin D ◽  
Mammary Gland ◽  
Reproductive Cycle ◽  
Mammary Gland Development ◽  
Metabolic Activation ◽  
Calcium Content ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Autocrine Signaling ◽  
Postlactational Involution ◽  
Gland Development

Abstract The vitamin D receptor (VDR) is present in mammary gland, and VDR ablation is associated with accelerated glandular development during puberty. VDR is a nuclear receptor whose ligand, 1,25-dihydroxyvitamin D [1,25-(OH)2D] is generated after metabolic activation of vitamin D by specific vitamin D hydroxylases. In these studies, we demonstrate that both the VDR and the vitamin D 1-α hydroxylase (CYP27B1), which produces 1,25-(OH)2D are present in mammary gland and dynamically regulated during pregnancy, lactation, and involution. Furthermore, we show that mice lacking VDR exhibit accelerated lobuloalveolar development and premature casein expression during pregnancy and delayed postlactational involution compared with mice with functional VDR. The delay in mammary gland regression after weaning of VDR knockout mice is associated with impaired apoptosis as demonstrated by reductions in terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling staining, caspase-3 activation and Bax induction. Under the conditions used in this study, VDR ablation was not associated with hypocalcemia, suggesting that altered mammary gland development in the absence of the VDR is not related to disturbances in calcium homeostasis. Furthermore, in the setting of normocalcemia, VDR ablation does not affect milk protein or calcium content. These studies suggest that the VDR contributes to mammary cell turnover during the reproductive cycle, and its effects may be mediated via both endocrine and autocrine signaling pathways. Unlike many mammary regulatory factors that exert transient, stage-specific effects, VDR signaling impacts on mammary gland biology during all phases of the reproductive cycle.

scholarly journals Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution

2003 ◽  
Vol 161 (1) ◽  
pp. 197-209 ◽  
Author(s):  
Susann Schenk ◽  
Edith Hintermann ◽  
Martin Bilban ◽  
Naohiko Koshikawa ◽  
Carlo Hojilla ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Tissue Remodeling ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Mitogen Activated Protein Kinase ◽  
Direct Stimulation ◽  
Laminin 5

Extracellular matrix (ECM) fragments or cryptic sites unmasked by proteinases have been postulated to affect tissue remodeling and cancer progression. Therefore, the elucidation of their identities and functions is of great interest. Here, we show that matrix metalloproteinases (MMPs) generate a domain (DIII) from the ECM macromolecule laminin-5. Binding of a recombinant DIII fragment to epidermal growth factor receptor stimulates downstream signaling (mitogen-activated protein kinase), MMP-2 gene expression, and cell migration. Appearance of this cryptic ECM ligand in remodeling mammary gland coincides with MMP-mediated involution in wild-type mice, but not in tissue inhibitor of metalloproteinase 3 (TIMP-3)–deficient mice, supporting physiological regulation of DIII liberation. These findings indicate that ECM cues may operate via direct stimulation of receptor tyrosine kinases in tissue remodeling, and possibly cancer invasion.

Targeted Expression of Activated Rac3 in Mammary Epithelium Leads to Defective Postlactational Involution and Benign Mammary Gland Lesions

2003 ◽  
Vol 175 (2) ◽  
pp. 72-83 ◽  
Author(s):  
Karen Leung ◽  
Andre Nagy ◽  
Ignacio Gonzalez-Gomez ◽  
John Groffen ◽  
Nora Heisterkamp ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Epithelium ◽  
Targeted Expression ◽  
Postlactational Involution
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