A theoretical model of type I collagen proteolysis by matrix metalloproteinase (MMP) 2 and membrane type 1 MMP in the presence of tissue inhibitor of metalloproteinase 2.

The Journal of Biological Chemistry
Emmanouil D Karagiannis, Aleksander S Popel

Abstract

One well documented family of enzymes responsible for the proteolytic processes that occur in the extracellular matrix is the soluble and membrane-associated matrix metalloproteinases. Here we present the first theoretical model of the biochemical network describing the proteolysis of collagen I by matrix metalloproteinases 2 (MMP2) and membrane type 1 matrix metalloproteinases (MT1-MMP) in the presence of the tissue inhibitor of metalloproteinases 2 (TIMP2) in a bulk, cell-free, well stirred environment. The model can serve as a tool for describing quantitatively the activation of the MMP2 proenzyme (pro-MMP2), the ectodomain shedding of MT1-MMP, and the collagenolysis arising from both of the enzymes. We show that pro-MMP2 activation, a process that involves a trimer formation of the proenzyme with TIMP2 and MT1-MMP, is suppressed at high inhibitor levels and paradoxically attains maximum only at intermediate TIMP2 concentrations. We also calculate the conditions for which pro-MMP2 activation is maximal. Furthermore we demonstrate that the ectodomain shedding of MT1-MMP can serve as a mechanism controlling the MT1-MMP availability and therefore the pro-MMP2 activation. Finally the proteolytic synergism of MMP2 and MT1-MMP is ...Continue Reading

References

Apr 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·J FangM A Moses
Oct 13, 2000·American Journal of Physiology. Cell Physiology·O PlatoshynJ X Yuan
Jun 27, 2002·Seminars in Cancer Biology·William HornebeckGeorges Bellon
Sep 17, 2002·Current Opinion in Cell Biology·Motoharu Seiki
Nov 14, 2002·Canadian Journal of Applied Physiology = Revue Canadienne De Physiologie Appliquée·Tara L Haas
Jun 13, 2003·Genome Biology·Robert P T SomervilleSuneel S Apte
Sep 12, 2003·American Journal of Physiology. Cell Physiology·Yong QianBing-Hua Jiang
Jun 3, 2004·Annals of Biomedical Engineering·Renee J Filion, Aleksander S Popel

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Citations

May 1, 2009·Histochemistry and Cell Biology·Baohua ZhangHongmei Wang
Mar 3, 2010·Annals of Biomedical Engineering·Dewi Harjanto, Muhammad H Zaman
May 19, 2011·Annals of Biomedical Engineering·Corban G RiveraAleksander S Popel
Nov 4, 2009·Nature Reviews. Cardiology·Ismail El-Hamamsy, Magdi H Yacoub
Nov 14, 2006·American Journal of Respiratory Cell and Molecular Biology·Wen NingAugustine M K Choi
Dec 20, 2007·Pediatric Research·Kazuyuki IkedaToshiro Hara
Jun 6, 2013·PLoS Computational Biology·Ayako WatanabeKazuhisa Ichikawa
Oct 8, 2011·PloS One·Alexandre DonzéPhilippe Tracqui
Apr 6, 2011·Theoretical Biology & Medical Modelling·Gang LiuAleksander S Popel
Aug 7, 2012·Theoretical Biology & Medical Modelling·Takashi SaitouTakashi Suzuki
Jan 4, 2012·Journal of Theoretical Biology·Takashi SaitouTakashi Suzuki
Dec 31, 2011·The Annals of Thoracic Surgery·John S IkonomidisJeffrey A Jones
Mar 10, 2016·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·L C LeeJ M Guccione
Apr 18, 2014·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Omid GhasemiYu-Fang Jin
Nov 19, 2013·Journal of Cellular and Molecular Medicine·Elizabeth A LogsdonFeilim Mac Gabhann
Apr 8, 2009·IEEE Engineering in Medicine and Biology Magazine : the Quarterly Magazine of the Engineering in Medicine & Biology Society·Amina A QutubAleksander S Popel
Apr 6, 2006·Matrix Biology : Journal of the International Society for Matrix Biology·Kevin WangLouis C Gerstenfeld
Oct 7, 2014·Drug Discovery Today·Stacey D FinleyAleksander S Popel
Mar 19, 2013·The American Journal of Pathology·Chun-Jun LiMing-Lin Liu
Jul 9, 2016·BMC Cancer·Chantel SamardzijaNuzhat Ahmed
Jul 24, 2007·The Journal of Pediatrics·Kenji FurunoToshiro Hara
Dec 22, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Hildur KnutsdottirEirikur Palsson
Jan 21, 2006·World Journal of Gastroenterology : WJG·Jian LiXiao-Hua Tao
Apr 4, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Lindsay E Clegg, Feilim Mac Gabhann
Aug 28, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Renee J Filion, Aleksander S Popel
May 19, 2010·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Anusuya DasRoger D Kamm
Aug 22, 2014·Diabetology & Metabolic Syndrome·Kei FukamiJosephine M Forbes
Jan 16, 2020·International Journal of Molecular Sciences·Olivera EvrovaJohanna Buschmann
Sep 13, 2007·The Journal of Biological Chemistry·Prakash VempatiAleksander S Popel
Feb 25, 2017·Bulletin of Mathematical Biology·Kenneth Y Wertheim, Tiina Roose
Apr 18, 2017·Proceedings. Mathematical, Physical, and Engineering Sciences·A-T VuongW A Wall
Jun 24, 2017·Computational and Mathematical Methods in Medicine·Shuji KawasakiTakashi Suzuki

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