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Remodeling of Zn(2+) Homeostasis Upon Differentiation of Mammary Epithelial Cells
- Publication Year :
- 2020
-
Abstract
- Zinc is the second most abundant transition metal in humans and an essential nutrient required for growth and development of newborns. During lactation, mammary epithelial cells differentiate into a secretory phenotype, uptake zinc from blood circulation, and export it into mother’s milk. At the cellular level, many zinc-dependent cellular processes, such as transcription, metabolism of nutrients, and proliferation are involved in the differentiation of mammary epithelial cells. Using mouse mammary epithelial cells as a model system, we investigated the remodeling of zinc homeostasis during differentiation induced by treatment with the lactogenic hormones cortisol and prolactin. RNA-Seq at different stages of differentiation revealed changes in global gene expression, including genes encoding zinc-dependent proteins and regulators of zinc homeostasis. Increases in mRNA levels of three zinc homeostasis genes, Slc39a14 (ZIP14) and metallothioneins (MTs) I and II were induced by cortisol but not by prolactin. The cortisol-induced increase was partially mediated by the nuclear glucocorticoid receptor signaling pathway. An increase in the cytosolic labile Zn2+ pool was also detected in lactating mammary cells, consistent with upregulation of MTs. We found that the zinc transporter ZIP14 was important for the expression of a major milk protein, whey acid protein (WAP), as knockdown of ZIP14 dramatically decreased WAP mRNA levels. In summary, our study demonstrated remodeling of zinc homeostasis upon differentiation of mammary epithelial cells resulting in changes in cytosolic Zn2+ and differential expression of zinc homeostasis genes, and these changes are important for establishing the lactation phenotype.
- Subjects :
- 0301 basic medicine
Hydrocortisone
Cations, Divalent
Cellular differentiation
Biophysics
Biochemistry
Article
Cell Line
Biomaterials
03 medical and health sciences
Mice
0302 clinical medicine
Mammary Glands, Animal
Downregulation and upregulation
Lactation
Gene expression
medicine
Animals
Homeostasis
Regulation of gene expression
Gene knockdown
Chemistry
Metals and Alloys
Cell Differentiation
Epithelial Cells
Prolactin
Cell biology
Zinc
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Female
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....9b5b1dc0e38450842271291522f80217