Title |
Matrix-metalloproteinase-9 is cleaved and activated by Cathepsin K
|
---|---|
Published in |
BMC Research Notes, July 2015
|
DOI | 10.1186/s13104-015-1284-8 |
Pubmed ID | |
Authors |
Jon Christensen, V Prasad Shastri |
Abstract |
Matrix-metalloproteinases 9 (MMP-9) belongs to the class of matrix metalloproteinases whose main function is to degrade and remodel the extracellular matrix (ECM). MMP-9 has been shown to be an integral part of many diseases where modulation of the ECM is a key step such as cancer, osteoporosis and fibrosis. MMP-9 is secreted as a latent pro-enzyme that requires activation in the extracellular space. Therefore, identifying physiological and molecular contexts, which can activate MMP-9 is important. Acidification of osteoclast-conditioned media to pH 5 resulted in a fragment with a size corresponding to active MMP-9. Also, treatment of recombinant proMMP-9 with recombinant cathepsin K (CTSK) at pH 5 yielded a fragment that corresponded to the molecular weight of active MMP-9, and showed MMP-9 activity. This activation was abrogated in the presence of CTSK inhibitor indicating that CTSK was responsible for the activation of pro-MMP-9. Knocking down CTSK in MDA-MB-231 cells also diminished MMP-9 activity compared to wild type control. Here we provide the first evidence that CTSK can cleave and activate MMP-9 in acidic environments such as seen in tumors and during bone resorption. This finding provides a key link between CTSK expression in tumors and bone and ECM remodeling, through MMP-9 activation. This novel mechanism to activate MMP-9 through extracellular physiological changes elucidated in this study reveals a protease-signaling network involving CTSK and MMP-9 and provides the impetus to explore ECM proteases as physiological markers and pharmacological targets. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
Germany | 1 | <1% |
Unknown | 140 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 22 | 15% |
Student > Bachelor | 22 | 15% |
Researcher | 17 | 12% |
Student > Master | 15 | 11% |
Student > Doctoral Student | 11 | 8% |
Other | 15 | 11% |
Unknown | 40 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 34 | 24% |
Agricultural and Biological Sciences | 22 | 15% |
Medicine and Dentistry | 15 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 7 | 5% |
Engineering | 5 | 4% |
Other | 12 | 8% |
Unknown | 47 | 33% |