Asymmetric expression of connexins between luminal epithelial- and myoepithelial- cells is essential for contractile function of the mammary gland.

摘要: Intercellular communication is essential for glandular functions and tissue homeostasis. Gap junctions couple cells homotypically heterotypically co-ordinate reciprocal responses between the different cell types. Connexins (Cxs) are main mammalian gap junction proteins, distribution of some Cx subtypes in heterotypic not symmetrical; murine mammary gland, Cx26, Cx30 Cx32 expressed only luminal epithelial Cx43 myoepithelial cells. Expression all four Cxs peaks during late pregnancy throughout lactation suggesting roles these proteins functional secretory activity gland. Transgenic (Tg) mice over-expressing Cx26 driven by keratin 5 promoter had an unexpected phenotype: mothers were unable to feed their pups weaning age leading litter starvation demise early mid-lactation. The gland K5-Cx26 female developed normally produced normal levels milk protein, a defect delivery rather than production. Because contained excessive milk, we hypothesized that may be inability eject milk. Using ex vivo three-dimensional organoid cultures, showed tissues isolated from wild-type FVB females contracted upon treatment with oxytocin, whereas, organoids Tg failed do so. Unexpectedly, found ectopic expression altered endogenous resulting impaired communication, demonstrated defective dye coupling mice. Inhibition or knock-down contraction response recapitulating observations glands We conclude acts as trans-dominant negative function cells, highlighting importance type-specific optimal contractile myoepithelium.