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Expression and Localization of Extracellular Matrix-Degrading Proteinases and Their Inhibitors in the Bovine Mammary Gland During Development, Function, and Involution

A. Rabot^*, F. Sinowatz, B. Berisha^*, H. H. D. Meyer^* and D. Schams^*,1

^* Physiology Weihenstephan, Technical University Munich, Weihenstephaner Berg 3, D-85350 Freising, Germany
Institute of Veterinary Anatomy, University of Munich, D-80539 Munich, Germany

¹ Corresponding author: physio{at}wzw.tum.de

In degrading the extracellular matrix, matrix metalloproteinases (MMP) and the plasminogen activator (PA) system may play a critical role in extensive remodeling that occurs in the bovine mammary gland during development, lactation, and involution. Therefore, the aim of our study was to investigate the mRNA expression of MMP-1, MMP-2, MMP-14, MMP-19, tissue inhibitor of metalloproteinases (TIMP)-1, TIMP-2, urokinase-type PA, tissue-type PA, urokinase-type PA receptor, and PA inhibitor-1 by quantitative PCR and to localize with immunohistochemistry MMP-1, MMP-2, MMP-14, and TIMP-2 proteins in the bovine mammary gland during pubertal mammogenesis, lactogenesis, galactopoiesis, and involution. Expression of mRNA for each of the studied factors was relatively lower during galactopoiesis and early involution but was markedly increased during mammogenesis and late involution, 2 stages in which tissue remodeling is especially pronounced. The localization of proteins for MMP-1, MMP-14, and TIMP-2 showed a similar trend with strong staining intensity in cytoplasm of mammary duct and alveolar epithelial cells during pubertal mammogenesis and late involution. Interestingly, MMP-2 protein was localized only in the cytoplasm of endothelial cells during late involution. Our study demonstrated clearly that expression of extracellular matrix-degrading proteinases coincides with a concomitant expression of their inhibitors. High expression levels of MMP, TIMP, and PA family members seem to be a typical feature of the nonlactating mammary gland.

Key Words: matrix metalloproteinases • plasminogen activator • mammary gland • bovine

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