Gingival fibroblast inhibits MMP-7: evaluation in an ex vivo aorta model.
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.
Gogly
Bruno
B
Paris-Descartes University, Paris-Descartes Medicine Faculty, INSERM U849, Paris, France.
Fournier
Benjamin
B
Couty
Ludovic
L
Naveau
Adrien
A
Brasselet
Camille
C
Durand
Eric
E
Coulomb
Bernard
B
Lafont
Antoine
A
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology*; D018920:Coculture Techniques; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011817:Rabbits; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D034741:RNA, Small Interfering; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D020783:Matrix Metalloproteinase 7