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- W2786402376 endingPage "e1007211" @default.
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- W2786402376 abstract "The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation." @default.
- W2786402376 created "2018-02-23" @default.
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- W2786402376 date "2018-02-08" @default.
- W2786402376 modified "2023-10-09" @default.
- W2786402376 title "Th-POK regulates mammary gland lactation through mTOR-SREBP pathway" @default.
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- W2786402376 doi "https://doi.org/10.1371/journal.pgen.1007211" @default.
- W2786402376 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5821406" @default.
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- W2786402376 hasPublicationYear "2018" @default.
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