The Role of Tight Junctions in Mammary Gland Function

Abstract

Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.

Genome wide association study identifies novel potential candidate genes for bovine milk cholesterol content

“…Meanwhile, cell-cell signaling (p = 0.001) and cell communication (p = 0.004) (Table 2) were among the most significant biological processes GO terms for CHL_fat suggesting that the regulation of CHL_fat probably requires the interaction and shared signaling activities between different cell types. Among the five KEGG pathways significantly enriched for CHL_fat positional candidate genes, the tight junction pathway has important roles in the transportation of milk constituents in mammary gland cells 52,53 , therefore it might also function in the transportation of CHL from the blood stream into the mammary gland or from mammary gland cells ( de novo synthesized) into milk. Focal adhesion is an important pathway for immune functions in bovine mammary cells 54 , for lactation involution 55 and for epigenetic regulation of milk production 56 .…”

Physiology of milk secretion

“…2D). TJs also delimit the apical (APM) from the basolateral (BPM) plasma membranes of MECs, thus contributing to the establishment and the maintenance of the functional asymmetry (polarity) of MECs required for the vectorial secretion of milk [34]. The basal side of alveolar MECs contacts myoepithelial cells and the basement membrane (BM), a specialized ECM, which separates the epithelium from the stroma and the vascular system.…”

Phenotypic and Molecular Alterations in the Mammary Tissue of R-Spondin1 Knock-Out Mice during Pregnancy

“…Changes to the morphology of mammary tissue were therefore investigated. Tight junctions, cellular structures that facilitate cell-cell communications, are important to maintaining the three-dimensional structure of the mammary epithelium [35]. By immune-labelling the protein constituents of tight junctions, Occludin and Zo-1, as well as the luminal and myoepithelial cell markers, E-cadherin and smooth muscle actin (α-SMA), we were able to show that the structure of the mammary epithelium was not modified in Rspo1 -/- mammary samples during pregnancy (S1 Fig).…”