Effect of Prostaglandin D2on mRNA Expression of Three Isoforms of Hyaluronic Acid Synthase in Nasal Polyp Fibroblasts

Background Hyaluronan is one of the major extracellular matrixes in chronic rhinosinusitis (CRS) associated with tissue remodeling. Prostaglandin D-2(PGD(2)) is also associated with the pathogenesis of CRS. However, little is known about whether PGD(2)regulates hyaluronan production by human airway fibroblasts. Objective We sought to determine the effect of PGD(2)on the mRNA expression of three isoforms of membrane-bound hyaluronic acid synthase (HAS1, HAS2 and HAS3) in fibroblasts, the major source of hyaluronan production, derived from CRS patients. Methods Nasal polyp-derived fibroblasts (NPDF) and uncinate tissue-derived fibroblasts (UTDF) were established from CRS patients with nasal polyps and those without, respectively. These fibroblasts were stimulated with PGD(2)or PGD(2)receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. mRNA levels for HAS1, HAS2 and HAS3 were determined by real-time quantitative PCR. Results PGD(2)(1 mu M) significantly enhanced HAS1 but not HAS2 or HAS3 mRNA expression by NPDF. Enhanced HAS1 mRNA expression was also obtained by stimulation with a DP receptor-selective agonist, but not with a CRTH2 receptor-selective agonist. In addition, PGD(2)-induced HAS1 mRNA expression was significantly inhibited by pre-treatment with DP receptor-selective antagonists. Similar induction of PGD(2)-induced HAS1 mRNA expression was seen in UTDF. Conclusion PGD(2)selectively stimulates HAS1 mRNA expression in local fibroblasts in CRS via DP, but not CRTH2, receptors.