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Gingival fibroblast inhibits MMP-7: evaluation in an ex vivo aorta model
Bruno Gogly1, Benjamin Fournier, Ludovic Couty
1Paris-Descartes University, Paris-Descartes Medicine Faculty, INSERM U849, Paris, France.
Abstract:
Matrix metalloproteinases (MMP) play a deleterious role in numerous vascular diseases. In contrast, gingival matrix remodelling is adequately regulated by the gingival fibroblast (GF). Here, we aimed to evaluate the GF activity on MMP-7 expression and secretion in coculture with aorta rings. We evaluated MMP-7 transcription and secretion in rabbit aorta rings cultured or not with gingival fibroblasts in collagen gels. GF induced an increase of TIMP-1 transcription and secretion, followed, similarly to other MMPs, by the formation of TIMP-1/MMP-7 complexes. There was also a decrease of MMP-7 mRNA by RT-PCR in aorta rings cocultured with gingival fibroblasts. Interestingly, in contrast with other MMPs (which were not influenced at a transcription level), GF stimulated the release of TGF-beta1, which in turn inhibited the transcription and synthesis of MMP-7, as shown by neutralizing MMP-7 inhibition due to gingival fibroblast by overexpressing decorin (a TGF beta 1 inhibitor) or by silencing TGF beta 1 using siRNA. We showed that healing properties of the GF could be transposed to another organ, i.e., ex vivo aneurism model, implicating a down-regulation of MMP-7.
Insights
Gingival fibroblasts (GF) can regulate matrix metalloproteinase-7 (MMP-7) in vascular tissue. GF promote healing by down-regulating MMP-7, suggesting potential therapeutic applications.
Area of Science:
- Vascular Biology
- Tissue Engineering
- Cell Biology
Background:
- Matrix metalloproteinases (MMPs) are implicated in vascular disease pathogenesis.
- Gingival fibroblasts (GF) possess matrix remodeling capabilities.
- Understanding GF-mediated regulation of MMPs is crucial for vascular health.
Purpose of the Study:
- To investigate the effect of GF on MMP-7 expression and secretion in vascular tissue.
- To explore the potential of GF in modulating vascular matrix remodeling.
Main Methods:
- Co-culture of rabbit aorta rings with GF in collagen gels.
- Assessment of MMP-7 and TIMP-1 transcription via RT-PCR.
- Quantification of MMP-7 and TIMP-1 secretion.
- Evaluation of TGF-beta1 involvement using decorin overexpression and siRNA silencing.
Main Results:
- GF increased TIMP-1 transcription and secretion, leading to TIMP-1/MMP-7 complex formation.
- GF co-culture decreased MMP-7 mRNA levels in aorta rings.
- GF stimulated TGF-beta1 release, which inhibited MMP-7 transcription and synthesis.
- Neutralization of TGF-beta1 or MMP-7 inhibition by GF was demonstrated.
Conclusions:
- Gingival fibroblasts can down-regulate MMP-7 expression and secretion in vascular tissue.
- GF exhibit healing properties transferable to vascular contexts, such as an ex vivo aneurysm model.
- TGF-beta1 signaling mediates the inhibitory effect of GF on MMP-7 in vascular cells.
