Culture of human dermal fibroblasts in the presence of hyaluronic acid and polyethylene glycol: effects on cell proliferation, collagen production, and related enzymes linked to the remodeling of the extracellular matrix

ABS TRACT Introduction: Cutaneous fillings are a common procedure in today’s dermatology, with the majority being carried out with hyaluronic acid isolated or combined with other substances. Objective: To study the effects of adding hyaluronic acid and polyethylene glycol to cultures of human dermal fibroblasts. Methods: The study evaluated: cell proliferation and production of type 1 collagen (COL1A1) in the presence or absence of anti-CD44 antibodies (membrane receptor for hyaluronic acid); the synthesis of metalloproteinase-1 (mmp-1), of tissue factor inhibitor of metalloproteinase-1 (TIMP1) and of transforming growth factor-α (TGF-α) through the analysis of gene expression via PCR (polymerase chain reaction); cell proliferation through the detection of the incorporation of a thymidine analogue in the cellular DNA. Results: Increased proliferation of fibroblasts and collagen synthesis were observed in the cultures exposed to hyaluronic acid, partially inhibited by the presence of anti-CD44 antibodies in the cultures. The exposure of cultures to hyaluronic acid enhances the production of TIMP-1 and TGFα, and reduces the expression of MMP-1. These effects were not noticed in the cultures exposed to polyethyene glycol. Conclusion: In an in vitro setting, the addition of hyaluronic acid to cultures of human dermal fibroblasts increases proliferation and synthesis of COL1A1, TIMP-1 and TGF-α, decreasing that of MMP-1. The addition of anti-CD44 to the cultures reduces cell proliferation and collagen synthesis, which may indicate the role of that receptor in mediating those events.