Modulation of human fibroblast gap junction intercellular communication by hyaluronan

J Cell Physiol. 2003 Jul;196(1):165-70. doi: 10.1002/jcp.10288.


The composition of the extracellular matrix changes during dermal repair. Initially, hyaluronan (HA) concentration is high, however, by day 3, HA is eliminated. HA optimizes collagen organization within granulation tissue. One possible mechanism of HA modulation of collagen packing is through the promotion of gap junction intercellular communication (GJIC). Gap junctions are gated channels that allow rapid intercellular communication and synchronization of coupled cell activities. The gap junction channel is composed of connexin (Cx) proteins that form a gated channel between coupled cells. HA is reported to enhance Cx43 expression in transformed fibroblasts. GJIC was quantified by the scrape loading technique and reported as a coupling index. The coupling index for human dermal fibroblasts was 4.6 +/- 0.2, while the coupling index for fibroblasts treated with HA more than doubled to 10.6 +/- 0.7. By Western blot analysis no differences were appreciated in the protein levels of Cx43 or beta-catenin, a protein involved in the translocation of Cx to the cell surface. By immuno-histology Cx43 and beta-catenin were evenly distributed throughout the cell in controls, but in cells treated with HA these proteins were co-localized to the cell surface. Coupled fibroblasts are reported to enhance the organization of collagen fibrils. It is proposed that HA increases the accumulation of Cx43 and beta-catenin on the cell surface, leading to greater GJIC and enhanced collagen organization.

MeSH terms

  • Cell Communication / drug effects*
  • Cells, Cultured
  • Dermis / cytology
  • Dermis / drug effects
  • Dermis / metabolism
  • Fibroblasts
  • Gap Junctions / drug effects*
  • Gap Junctions / metabolism*
  • Humans
  • Hyaluronic Acid / pharmacology*


  • Hyaluronic Acid