TY - JOUR
T1 - Effect of Prostaglandin D2 on mRNA Expression of Three Isoforms of Hyaluronic Acid Synthase in Nasal Polyp Fibroblasts
AU - Hirata, Yuji
AU - Kariya, Shin
AU - Kanai, Kengo
AU - Fujiwara, Tazuko
AU - Makihara, Sei Ichiro
AU - Omichi, Ryotaro
AU - Higaki, Takaya
AU - Haruna, Takenori
AU - Oka, Aiko
AU - Nishizaki, Kazunori
AU - Okano, Mitsuhiro
N1 - Funding Information:
The authors would like to thank Yuko Okano for her editorial assistance. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by grants from Ministry of Education, Culture, Sports, Science and Technology, Japan (16K15721 and 17K16920) and grants from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP17ek0410040, and JP16ek0109062.
Publisher Copyright:
© The Author(s) 2020.
PY - 2021/1
Y1 - 2021/1
N2 - Background: Hyaluronan is one of the major extracellular matrixes in chronic rhinosinusitis (CRS) associated with tissue remodeling. Prostaglandin D2 (PGD2) is also associated with the pathogenesis of CRS. However, little is known about whether PGD2 regulates hyaluronan production by human airway fibroblasts. Objective: We sought to determine the effect of PGD2 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 PGD2 or PGD2 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: PGD2 (1 µM) 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, PGD2-induced HAS1 mRNA expression was significantly inhibited by pre-treatment with DP receptor-selective antagonists. Similar induction of PGD2-induced HAS1 mRNA expression was seen in UTDF. Conclusion: PGD2 selectively stimulates HAS1 mRNA expression in local fibroblasts in CRS via DP, but not CRTH2, receptors.
AB - Background: Hyaluronan is one of the major extracellular matrixes in chronic rhinosinusitis (CRS) associated with tissue remodeling. Prostaglandin D2 (PGD2) is also associated with the pathogenesis of CRS. However, little is known about whether PGD2 regulates hyaluronan production by human airway fibroblasts. Objective: We sought to determine the effect of PGD2 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 PGD2 or PGD2 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: PGD2 (1 µM) 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, PGD2-induced HAS1 mRNA expression was significantly inhibited by pre-treatment with DP receptor-selective antagonists. Similar induction of PGD2-induced HAS1 mRNA expression was seen in UTDF. Conclusion: PGD2 selectively stimulates HAS1 mRNA expression in local fibroblasts in CRS via DP, but not CRTH2, receptors.
KW - DP
KW - PGD2
KW - chronic rhinosinusitis
KW - fibroblast
KW - hyaluronic acid synthase
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U2 - 10.1177/1945892420932781
DO - 10.1177/1945892420932781
M3 - Article
C2 - 32551924
AN - SCOPUS:85086647085
SN - 1945-8924
VL - 35
SP - 44
EP - 51
JO - American Journal of Rhinology and Allergy
JF - American Journal of Rhinology and Allergy
IS - 1
ER -