Differences in the expression of glycosaminoglycans in human fibroblasts derived from gingival overgrowths is related to TGF-beta up-regulation

Abstract

Glycosaminoglycans (GAGs) play important roles in cell behavior and have the ability to bind and modulate cytokines. Using primary cultured fibroblasts from hereditary gingival fibromatosis (HGF), normal gingiva (NG), and NG treated with cyclosporin-A (NGc) we show changes in the expression and structural characteristics of GAGs as well as in the expression of enzymes involved in their biosynthesis and degradation. In addition, we show the over-expression of TGF-β1 and TGF-β type II receptor in HGF and NGc. There is an increase in the GAGs retained in the cellular fraction, and the fine structure of galactosaminoglycans show a decrease in α-l-iduronic acid content in HGF and NGc. Elevated extracellular levels of low molecular weight hyaluronan (HA) are found in HGF due to increase in the expression of HA synthase 3 and hyaluronidases 1 and 2. The results bring new insights to the accumulation of extracellular matrix related to TGF-β over-expression.

Keywords::

• Sulfated glycosaminoglycans
• hyaluronan
• growth factors
• hyaluronan synthases
• hyaluronidases

Acknowledgements

This work was supported by Brazilian grant agencies (FAPESP, CNPq, CAPES). J. L. Dreyfuss is sponsored by Jairo Ramos postdoctoral fellowship awarded by FAP UNIFESP (Fundação de Apoio a Pesquisa).

We are indebted to Aline Mendes, M.Sc. and Elsa Y. Kobayashi, M.Sc. for technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.