The expression and localization of extracellular matrix-degrading proteases in the mammary gland during development, function and involution in the cow

Extracellular matrix (ECM) degrading proteases, like matrix metalloproteases (MMP) and the plasminogen activator (PA) system may play a critical role in extensive remodelling 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 (u)PA, tissue type (t)PA, uPA receptor (uPAR) and PA inhibitor-1 (PAI-1) by quantitative real-time PCR (Rotor-Gene) and to localize with immunohistochemistry MMP-1, MMP-2, MMP-14, and TIMP-2 proteins in 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, two stages where 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 only localized in cytoplasm of endothelial cells during late involution. Our study demonstrated clearly that expression of extracellular matrix-degrading proteases 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 non-lactating mammary gland.

Supported by DFG (Scha 257/13–3).