Prostaglandin D₂ Inhibits Collagen Secretion From Lung Fibroblasts by Activating the DP Receptor Prostaglandin D_2 Inhibits Collagen Secretion From Lung Fibroblasts by Activating the DP Receptor

Access this Article

Author(s)

    • Ayabe Shinya AYABE Shinya
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
    • Kida Taiki KIDA Taiki
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
    • OZAKI Hiroshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
    • MURATA Takahisa
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo

Abstract

Lung fibroblasts are responsible for collagen secretion during normal tissue repair and the development of fibrosis. Many other prostaglandins have been reported to regulate collagen synthesis in lung fibroblasts, but the role of prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) is unknown. In this study, we investigated the effect of PGD<sub>2</sub> on type I collagen secretion in human lung fibroblasts. Pretreatment with PGD<sub>2</sub> (0.1 - 10 <i>μ</i>M, 1 h) significantly attenuated type I collagen secretion to the cell supernatant induced by transforming growth factor-<i>β</i> (TGF-<i>β</i>). Although an agonist on chemoattractant receptorhomologous molecule expressed on Th2 cells (CRTH2) did not have any effect, the prostanoid DP-receptor agonist BW245C (0.01 - 1 <i>μ</i>M) suppressed TGF-<i>β</i>-induced collagen secretion. PGD<sub>2</sub> and BW245C significantly increased intracellular cAMP level. One-hour pretreatment with forskolin (0.1 - 10 <i>μ</i>M), dibutyryl-cAMP (0.01 - 1 mM), and the protein kinase A (PKA)-activator <i>N</i><sup>6</sup>-phenyl-cyclic AMP (100 <i>μ</i>M) significantly reduced TGF-<i>β</i>-induced collagen secretion, while exchange protein activated by cAMP (Epac) activator 8-bromo-2′-<i>O</i>-methyladenosine-3′,5′-cyclic AMP (10 <i>μ</i>M) did not affect collagen deposition. These results suggest that PGD<sub>2</sub> inhibits TGF-<i>β</i>-induced collagen secretion via intracellular cAMP accumulation through activating DP receptor.

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 121(4), 312-317, 2013-04-20

    The Japanese Pharmacological Society

References:  29

Codes

  • NII Article ID (NAID)
    10031171141
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    13478613
  • NDL Article ID
    024434313
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
Page Top