TY - JOUR
T1 - Lipocalin-type prostaglandin D synthase as a regulator of the retinoic acid signalling in melanocytes
AU - Takeda, Kazuhisa
AU - Takahashi, Na Ho
AU - Yoshizawa, Miki
AU - Shibahara, Shigeki
N1 - Funding Information:
Grants-in-aid for Scientific Research (B) (to S.S.); Scientific Research (C) (to K.T.) from the Ministry of Education, Science, Sports and Culture of Japan.
PY - 2010/8
Y1 - 2010/8
N2 - 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 μM) 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.
AB - 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 μM) 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.
KW - all-trans retinoic acid
KW - lipocalin-type prostaglandin D synthase
KW - melanocytes
KW - melanoma
KW - proliferation
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U2 - 10.1093/jb/mvq040
DO - 10.1093/jb/mvq040
M3 - Article
C2 - 20403807
AN - SCOPUS:77955183841
VL - 148
SP - 139
EP - 148
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 2
ER -