Lipocalin-type prostaglandin D synthase as a regulator of the retinoic acid signalling in melanocytes.
Lipocalin-type prostaglandin D synthase (L-PGDS) catalyses the formation of prostaglandin D(2) (PGD(2)) and also functions as a transporter for lipophilic ligands, including all-trans retinoic acid (RA). Here, we show that human epidermal melanocytes produce and secrete L-PGDS and PGD(2) in culture medium, whereas L-PGDS is not expressed in human melanoma cell lines, HMV-II, SK-MEL-28, 624 mel and G361. Treatment with RA (1 or 10 microM) for 4 days decreased the proliferation of melanocytes (30% decrease), but not melanoma cells. We therefore isolated L-PGDS-expressing cell lines from 624 mel cells. Treatment with RA decreased the proliferation of L-PGDS-expressing cells by 20%, but not mock-transfected cell lines lacking L-PGDS expression. RA induced expression of a cyclin-dependent kinase inhibitor p21(Cip1) in L-PGDS-expressing cells, but not mock-transfected cells. Moreover, RA increased the transient expression of a reporter gene carrying the RA-responsive elements in L-PGDS-expressing cell lines (at least 5-fold activation), compared to the 2-fold activation in mock-transfected cell lines, suggesting that L-PGDS may increase the sensitivity to RA. Lastly, the knockdown of L-PGDS expression by RNA interference was associated with the restoration of the RA-mediated decrease in proliferation of human and mouse melanocytes. In conclusion, L-PGDS may fine-tune the RA signalling in melanocytes.
Takeda
Kazuhisa
K
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan. ktakeda@m.tains.tohoku.ac.jp
Takahashi
Na-Ho
NH
Yoshizawa
Miki
M
Shibahara
Shigeki
S
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000502:physiology*; D054834:Lipocalins / Q000502:physiology*; D008544:Melanocytes / Q000378:metabolism / Q000502:physiology*; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D014212:Tretinoin / Q000502:physiology
D054834:Lipocalins; D014212:Tretinoin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase