Sodium (Na+) can accumulate in the skin tissue, sequestered by negatively charged
glycosaminoglycans (GAGs). During dietary salt overload, the amount and charge density
of dermal GAG molecules – e.g., hyaluronic acid (HA) and chondroitin sulfate (CS)
– increases; however, the regulation of the process is unknown. Previously, it has
been demonstrated that the level of cyclooxygenase-2 (COX-2) activity and the content
of prostaglandin E2 (PGE2) are elevated in the skin due to high-salt consumption.
A link between the COX-2/PGE2 system and GAG synthesis was also suggested. We hypothesized
that in dermal fibroblasts (DFs) high-sodium concentration activates the COX-2/PGE2
pathway and also that PGE2 increases the production of HA. Our further aim was to
demonstrate that the elevation of the GAG content is ceased by COX-2 inhibition in
a salt overloaded animal model. For this, we investigated the messenger RNA (mRNA)
expression of COX-2 and HA synthase 2 enzymes as well as the PGE2 and HA production
of DFs by real-time reverse transcription PCR (qRT-PCR) and ELISA, respectively. The
results showed that both high-sodium concentration and PGE2 treatment increases HA
content of the media. Sodium excess activates the COX-2/PGE2 pathway in DFs, and COX-2
inhibition decreases the synthesis of HA. In the animal experiment, the HA- and CS
disaccharide content in the skin of male Wistar rats was measured using high performance
liquid chromatography-mass spectrometry (HPLC-MS). In the skin of rats receiving high-salt
diet, the content of both HA‐ and monosulfated-CS disaccharides increased, whereas
COX-2 inhibition blocked this overproduction. In conclusion, high-salt environment
could induce GAG production of DFs in a COX-2/PGE2-dependent manner. Moreover, the
COX-2 inhibition resulted in a decreased skin GAG content of the salt overloaded rats.
These data revealed a new DF-mediated regulation of GAG synthesis in the skin during
salt overload.
