BACKGROUND: The "non-animal stabilized hyaluronic acid" (NASHA) is a widely used product in bio-revitalization injective procedures in esthetic medicine. The present research aimed to quantitatively evaluate the therapeutic effect of one of the more used bio-revitalization products on cultured dermal fibroblasts. RT-PCR was used for gene expression profiling of some proteins known to be relevant in skin homeostasis. METHODS: Human dermal fibroblasts were seeded on a culture medium enriched with a product for dermal bio-revitalization, consisting of stabilized hyaluronic acid gel 20 mg/ml. After 24, 48, and 72 h of exposure, the cDNA was amplified by real-time PCR. Gene expression was quantified with the delta/delta calculation method. RESULTS: In this study, the gene of metalloproteinase (MMP)-13 is strongly expressed after NASHA incubation. The MMP-2 encoding gene instead is less expressed, but both evidence the same temporal trend, being progressively up-regulated after 24 and 48 h, thereafter the expression decreases, whereas MMP-3 maintains the same up-regulation at 72 h. Hyaluronan synthase 1 and desmoplakin are progressively up-regulated and increase at 24, 48, and 72 h. Hyaluronidase 1 and neutrophil elastase genes are overexpressed, but at 72 h they both exhibit the same behavior as the other degradative enzymes MMP-13 and MMP-2. CONCLUSIONS: Skin bio-revitalization by injecting the tested NASHA gel produces an enhancement in the expression of some genes involved in extracellular matrix degradation and organization. In this study, a time-dependent behavior, different for genes encoding degradative compared to synthesis proteins, was demonstrated.