Gingival fibroblast inhibits MMP-7: evaluation in an ex vivo aorta model

J Mol Cell Cardiol. 2009 Aug;47(2):296-303. doi: 10.1016/j.yjmcc.2009.04.012. Epub 2009 May 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Aorta / cytology
  • Aorta / enzymology*
  • Coculture Techniques
  • Decorin
  • Extracellular Matrix Proteins / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / enzymology*
  • Gingiva / cytology*
  • Humans
  • Matrix Metalloproteinase 7 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Proteoglycans / metabolism
  • RNA, Small Interfering / metabolism
  • Rabbits
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transcription, Genetic
  • Transfection
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / metabolism

Substances

  • DCN protein, human
  • Decorin
  • Extracellular Matrix Proteins
  • Matrix Metalloproteinase Inhibitors
  • Proteoglycans
  • RNA, Small Interfering
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinase 7