Takeda Kazuhisa, Yokoyama Satoru, Aburatani Hiroyuki, Masuda Takayuki, Han Feng, Yoshizawa Miki, Yamaki Naomi, Yamamoto Hiroaki, Eguchi Naomi, Urade Yoshihiro, Shibahara Shigeki
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Japan.
Biochem Biophys Res Commun. 2006 Jan 27;339(4):1098-106. doi: 10.1016/j.bbrc.2005.11.125. Epub 2005 Dec 5.
Microphthalmia-associated transcription factor (MITF) is responsible for differentiation of melanocytes. A recessive MITF mutant, black-eyed white Mitf(mi-bw) mouse, is characterized by white coat color and deafness, due to the lack of melanocytes in the skin and inner ears. By cDNA microarray analysis, we have identified lipocalin-type prostaglandin D synthase (L-PGDS), whose mRNA is undetectable in the homozygous Mitf(mi-bw) skin. Immunohistochemical analysis of wild-type mice identified the specific expression of L-PGDS in follicular melanocytes. L-PGDS mRNA is expressed in B16 mouse melanoma cells, but undetectable in human melanoma cell lines. RNA interference analysis against MITF suggests that L-PGDS expression is dependent on MITF in B16 melanoma cells. Furthermore, we have provided evidence that MITF is involved in the melanocyte lineage-specific transcription of the mouse L-PGDS gene. Thus, L-PGDS represents a newly identified melanocyte marker. MITF may modulate the production of prostaglandin D(2) by activating the L-PGDS gene in melanocytes.
小眼相关转录因子(MITF)负责黑素细胞的分化。一种隐性MITF突变体,即黑眼白色Mitf(mi-bw)小鼠,其特征是被毛白色且耳聋,这是由于皮肤和内耳中缺乏黑素细胞所致。通过cDNA微阵列分析,我们鉴定出了脂质运载蛋白型前列腺素D合成酶(L-PGDS),其mRNA在纯合Mitf(mi-bw)皮肤中无法检测到。对野生型小鼠的免疫组织化学分析确定了L-PGDS在毛囊黑素细胞中的特异性表达。L-PGDS mRNA在B16小鼠黑色素瘤细胞中表达,但在人黑色素瘤细胞系中无法检测到。针对MITF的RNA干扰分析表明,在B16黑色素瘤细胞中L-PGDS的表达依赖于MITF。此外,我们已经提供证据表明MITF参与了小鼠L-PGDS基因的黑素细胞谱系特异性转录。因此,L-PGDS代表一种新鉴定出的黑素细胞标志物。MITF可能通过激活黑素细胞中的L-PGDS基因来调节前列腺素D2的产生。