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RECK suppresses interleukin-17/TRAF3IP2-mediated MMP-13 activation and human aortic smooth muscle cell migration and proliferation.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2019 Dec; Vol. 234 (12), pp. 22242-22259. Date of Electronic Publication: 2019 May 09. - Publication Year :
- 2019
-
Abstract
- Sustained inflammation and matrix metalloproteinase (MMP) activation contribute to vascular occlusive/proliferative disorders. Interleukin-17 (IL-17) is a proinflammatory cytokine that signals mainly via TRAF3 Interacting Protein 2 (TRAF3IP2), an upstream regulator of various critical transcription factors, including AP-1 and NF-κB. Reversion inducing cysteine rich protein with kazal motifs (RECK) is a membrane-anchored MMP inhibitor. Here we investigated whether IL-17A/TRAF3IP2 signaling promotes MMP-13-dependent human aortic smooth muscle cell (SMC) proliferation and migration, and determined whether RECK overexpression blunts these responses. Indeed, IL-17A treatment induced (a) JNK, p38 MAPK, AP-1, NF-κB, and CREB activation, (b) miR-21 induction, (c) miR-27b and miR-320 inhibition, (d) MMP-13 expression and activation, (e) RECK suppression, and (f) SMC migration and proliferation, all in a TRAF3IP2-dependent manner. In fact, gain of TRAG3IP2 function, by itself, induced MMP-13 expression and activation, and RECK suppression. Furthermore, treatment with recombinant MMP-13 stimulated SMC migration in part via ERK activation. Importantly, RECK gain-of-function attenuated MMP-13 activity without affecting its mRNA or protein levels, and inhibited IL-17A- and MMP-13-induced SMC migration. These results indicate that increased MMP-13 and decreased RECK contribute to IL-17A-induced TRAF3IP2-dependent SMC migration and proliferation, and suggest that TRAF3IP2 inhibitors or RECK inducers have the potential to block the progression of neointimal thickening in hyperplastic vascular diseases.<br /> (© 2019 Wiley Periodicals, Inc.)
- Subjects :
- Cell Proliferation
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases metabolism
Humans
MicroRNAs genetics
MicroRNAs metabolism
Models, Biological
Recombinant Proteins metabolism
Regulatory Sequences, Nucleic Acid genetics
Signal Transduction
Vascular Diseases metabolism
Vascular Diseases pathology
Adaptor Proteins, Signal Transducing metabolism
Aorta cytology
Cell Movement
GPI-Linked Proteins metabolism
Interleukin-17 metabolism
Matrix Metalloproteinase 13 metabolism
Myocytes, Smooth Muscle cytology
Myocytes, Smooth Muscle metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 234
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 31074012
- Full Text :
- https://doi.org/10.1002/jcp.28792