Regulation of tight junction proteins during engorgement of the mammary gland : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University, Palmerston North, New Zealand

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dc.contributor.authorCooper Phyn, Claire Vanessa
dc.date.accessioned2010-08-20T01:33:37Z
dc.date.availableNO_RESTRICTIONen_US
dc.date.available2010-08-20T01:33:37Z
dc.date.issued2006
dc.descriptionContent removed due to copyright restriction: Appendix 6 Cooper, C. V., Stelwagen, K., Singh, K., Farr, V. C., Prosser, C. G., and Davis, S. R. (2004): Expression of the tight junction protein zonula occludens-1 during mammary engorgement. Proceedings of the New Zealand Society of Animal Production 64,43-47. Singh, K., Dobson, J., Phyn, C. V. C., Davis, S. R., Farr, V. C., Molenaar, A. J., and Stelwagen, K. (2005): Milk accumulation decreases expression of genes involved in cell-extracellular matrix communication and is associated with induction of apoptosis in the bovine mammary gland. Livestock Production Science 98,67-78. Appendix 7 McMahon, C.D., Farr, V.C., Singh, K., Wheeler, T.T. and Davis, S.R. (2004). Decreased expression of ß1-integrin and focal adhesion kinase in epithelial cells may initiate involution of mammary glands. Journal of Cellular Physiology 200, 318-325en_US
dc.description.abstractExtended periods of milk accumulation result in loss of secretory activity, increased apoptosis and eventually, involution of mammary glands. This process is associated with increased permeability of the tight junction (TJ) complexes between adjacent mammary epithelial cells (MECs). The change in cell shape during mammary engorgement from a cuboidal to a flattened morphology may initiate changes in protein and gene expression (mechanotransduction) that trigger these processes. Therefore, this study examined the regulation of the major TJ protein components during mammary engorgement, and in particular the role of physical distension of the mammary epithelium in the regulatory process. Expression of the integral transmembrane TJ proteins, occludin and claudin-1, and the cytoplasmic TJ protein, ZO-1, were down-regulated in both bovine and rat mammary glands during the early stages of mammary apoptosis and involution following the abrupt cessation of milk removal. In the rat, these responses were locally regulated as they occurred only in teat-sealed glands in a hemi-suckled model. Furthermore, the down-regulation of TJ proteins is consistent with a loss of TJ integrity during mammary engorgement. Induced physical distension of rat mammary glands in vivo transiently up-regulated the expression levels of occludin protein and mRNA, and ZO-1 mRNA, followed by an accelerated decrease in expression compared with the effects of milk accumulation alone. This was associated with the initiation of apoptosis, the up-regulation of the pro-apoptotic factor pSTAT3, and the down-regulation of the cell-ECM survival factor βl-integrin. An in vitro model was also developed to stretch MECs, mimicking the flattening in cell shape during mammary engorgement in vivo. While stretching MECs in vitro did not conclusively alter TJ protein expression, the overall results of this project support further investigation into the role of the TJ complex in mechanotransduction pathways. In addition, the results point to crosstalk between cell-ECM survival signalling and STAT3 death signalling as a candidate for regulation by physical distension of the mammary epithelium. In conclusion, this study supports the hypothesis that physical distension during engorgement of the mammary glands with milk is a primary trigger initiating apoptosis of MECs through changes in the regulation of gene pathways controlling cell survival and death, and the disruption of TJ function.en_US
dc.identifier.urihttp://hdl.handle.net/10179/1572
dc.language.isoenen_US
dc.publisherMassey Universityen_US
dc.rightsThe Authoren_US
dc.subjectMammary epithelial cellsen_US
dc.subjectApoptosisen_US
dc.subject.otherFields of Research::270000 Biological Sciences::270600 Physiology::270602 Animal physiology-cellen_US
dc.titleRegulation of tight junction proteins during engorgement of the mammary gland : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University, Palmerston North, New Zealanden_US
dc.typeThesisen_US
massey.contributor.authorCooper Phyn, Claire Vanessa
thesis.degree.disciplineAnimal Scienceen_US
thesis.degree.grantorMassey Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US
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