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Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF

(2013) EMBO MOLECULAR MEDICINE. 5(7). p.1000-1016
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Abstract
Several pathological processes, such as sepsis and inflammatory bowel disease (IBD), are associated with impairment of intestinal epithelial barrier. Here, we investigated the role of matrix metalloproteinase MMP13 in these diseases. We observed that MMP13(-/-) mice display a strong protection in LPS- and caecal ligation and puncture-induced sepsis. We could attribute this protection to reduced LPS-induced goblet cell depletion, endoplasmic reticulum stress, permeability and tight junction destabilization in the gut of MMP13(-/-) mice compared to MMP13(+/+) mice. Both in vitro and in vivo, we found that MMP13 is able to cleave pro-TNF into bioactive TNF. By LC-MS/MS, we identified three MMP13 cleavage sites, which proves that MMP13 is an alternative TNF sheddase next to the TNF converting enzyme TACE. Similarly, we found that the same mechanism was responsible for the observed protection of the MMP13(-/-) mice in a mouse model of DSS-induced colitis. We identified MMP13 as an important mediator in sepsis and IBD via the shedding of TNF. Hence, we propose MMP13 as a novel drug target for diseases in which damage to the gut is essential.
Keywords
intestinal permeability, matrix metalloproteinase, IBD, sepsis, tumour necrosis factor, NECROSIS-FACTOR-ALPHA, POLYMYXIN-B HEMOPERFUSION, SULFATE-INDUCED COLITIS, BOWEL-DISEASE, IN-VITRO, BACTERIAL TRANSLOCATION, MMP-13 EXPRESSION, TIGHT JUNCTIONS, UP-REGULATION, SEPTIC SHOCK

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Chicago
Vandenbroucke, Roosmarijn, Eline Dejonckheere, Filip Van Hauwermeiren, Sofie Lodens, Riet De Rycke, Elien Van Wonterghem, An Staes, Kris Gevaert, Carlos López-Otin, and Claude Libert. 2013. “Matrix Metalloproteinase 13 Modulates Intestinal Epithelial Barrier Integrity in Inflammatory Diseases by Activating TNF.” Embo Molecular Medicine 5 (7): 1000–1016.
APA
Vandenbroucke, Roosmarijn, Dejonckheere, E., Van Hauwermeiren, F., Lodens, S., De Rycke, R., Van Wonterghem, E., Staes, A., et al. (2013). Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF. EMBO MOLECULAR MEDICINE, 5(7), 1000–1016.
Vancouver
1.
Vandenbroucke R, Dejonckheere E, Van Hauwermeiren F, Lodens S, De Rycke R, Van Wonterghem E, et al. Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF. EMBO MOLECULAR MEDICINE. 2013;5(7):1000–16.
MLA
Vandenbroucke, Roosmarijn, Eline Dejonckheere, Filip Van Hauwermeiren, et al. “Matrix Metalloproteinase 13 Modulates Intestinal Epithelial Barrier Integrity in Inflammatory Diseases by Activating TNF.” EMBO MOLECULAR MEDICINE 5.7 (2013): 1000–1016. Print.
@article{4191286,
  abstract     = {Several pathological processes, such as sepsis and inflammatory bowel disease (IBD), are associated with impairment of intestinal epithelial barrier. Here, we investigated the role of matrix metalloproteinase MMP13 in these diseases. We observed that MMP13(-/-) mice display a strong protection in LPS- and caecal ligation and puncture-induced sepsis. We could attribute this protection to reduced LPS-induced goblet cell depletion, endoplasmic reticulum stress, permeability and tight junction destabilization in the gut of MMP13(-/-) mice compared to MMP13(+/+) mice. Both in vitro and in vivo, we found that MMP13 is able to cleave pro-TNF into bioactive TNF. By LC-MS/MS, we identified three MMP13 cleavage sites, which proves that MMP13 is an alternative TNF sheddase next to the TNF converting enzyme TACE. Similarly, we found that the same mechanism was responsible for the observed protection of the MMP13(-/-) mice in a mouse model of DSS-induced colitis. We identified MMP13 as an important mediator in sepsis and IBD via the shedding of TNF. Hence, we propose MMP13 as a novel drug target for diseases in which damage to the gut is essential.},
  author       = {Vandenbroucke, Roosmarijn and Dejonckheere, Eline and Van Hauwermeiren, Filip and Lodens, Sofie and De Rycke, Riet and Van Wonterghem, Elien and Staes, An and Gevaert, Kris and L{\'o}pez-Otin, Carlos and Libert, Claude},
  issn         = {1757-4676},
  journal      = {EMBO MOLECULAR MEDICINE},
  language     = {eng},
  number       = {7},
  pages        = {1000--1016},
  title        = {Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF},
  url          = {http://dx.doi.org/10.1002/emmm.201202100},
  volume       = {5},
  year         = {2013},
}

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