Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: Matrix metalloproteinase 9 (MMP9) has been implicated in extracellular matrix (ECM) remodelling, angiogenesis and inflammation. However, the targets for proteolysis that lead to these physiological consequences are often undefined as is the regulation of MMP9 itself. Therefore, identification of both the potential direct and indirect targets of MMP9 is critical for further understanding the effects of its proteolytic cascades. METHODS: To study these cascades on a wider scale, transgenic mouse "knock-out" models and ultra-high performance liquid chromatography mass spectroscopy (UPLC-MS(E) ) were used to elucidate the MMP9 targets, inhibitors, and interactors found in mouse seminal vesicle fluid (SVF). RESULTS: Proteomics analysis of SVF from wild type, mmp9-/- or pn1-/- mice detected differences in serine protease inhibitors (serpins), reproductive proteins, developmental regulators, and cancer proto-oncogenes, including Renin 1/2. Protease nexin 1 (PN1), an ECM-based inhibitor of urokinase, was elevated in the SVF of mmp9-/- mice. We observed that MMP9-mediated N-terminal cleavage of PN1 reduces this serpin's functional activity. Our data also suggest a feedback loop in which inhibition of PN1 is a critical step in permitting greater activity of MMP9. CONCLUSION: This study extends the degradome of MMP9 and examines components relevant to seminal fluid physiology. PN1 is proposed to be a novel inhibitor of MMP9 activity and a block to collagen cleavage, a frequent antecedent to cancer cell invasion. The interaction of MMP9 with PN1 and other serpins may lead to a better understanding of seminal vesicle function and possible impacts on fertility, as well as provide novel therapeutic targets.

Original publication




Journal article



Publication Date





1427 - 1440


metalloproteinase 9, protease nexin 1, seminal fluid, proteomics, Animals, Male, Matrix Metalloproteinase 9, Mice, Mice, Knockout, Proteolysis, Proteomics, Semen, Seminal Vesicles, Serpin E2