Lipin-1 expression is critical for keratinocyte differentiation
Lipin-1 expression is critical for keratinocyte differentiation
复制标题
DOI：
10.1194/jlr.m062588
复制
发表时间：
2016-04-01
影响因子：
6.5
通讯作者：
Shin, Dong Wook
中科院分区：
文献类型：
--
作者：
Chae, Minjung;Jung, Ji-Yong;Shin, Dong Wook
Lipin-1是一种Mg 2+依赖性磷脂酸磷酸酶，可促进磷脂酸脱磷酸化生成二酰甘油。Lipin-1在正常人表皮角质形成细胞（NHEK）中的表达和功能知之甚少。在这里，我们表明，脂蛋白-1是存在于基底和棘层的正常人表皮，脂蛋白-1的表达逐渐下调NHEK分化过程中。有趣的是，脂蛋白-1敲低（KD）抑制角质形成细胞分化，并通过上调p21表达引起G1期阻滞。角质形成细胞的分化需要p21的细胞周期阻滞，但必须下调角质形成细胞分化的进展。因此，减少角质形成细胞分化的结果从p21的持续上调脂蛋白-1 KD。Lipin-1 KD还降低蛋白激酶C（PKC）α的磷酸化/活化，而Lipin-1过表达增加PKC α磷酸化。用PKC α抑制剂，如lipin-1 KD，刺激p21表达，而lipin-1过表达减少p21表达，暗示PKC α在lipin-1诱导的p21表达调节中。两者合计，这些结果表明，脂蛋白-1介导的下调p21的角质形成细胞分化的进展后，角质形成细胞的分化诱导的p21的初步承诺是至关重要的，和PKC α参与p21的表达调节脂蛋白-1。
Lipin-1 is an Mg2+-dependent phosphatidate phosphatase that facilitates the dephosphorylation of phosphatidic acid to generate diacylglycerol. Little is known about the expression and function of lipin-1 in normal human epidermal keratinocytes (NHEKs). Here, we demonstrate that lipin-1 is present in basal and spinous layers of the normal human epidermis, and lipin-1 expression is gradually downregulated during NHEK differentiation. Interestingly, lipin-1 knockdown (KD) inhibited keratinocyte differentiation and caused G1 arrest by upregulating p21 expression. Cell cycle arrest by p21 is required for commitment of keratinocytes to differentiation, but must be downregulated for the progress of keratinocyte differentiation. Therefore, reduced keratinocyte differentiation results from sustained upregulation of p21 by lipin-1 KD. Lipin-1 KD also decreased the phosphorylation/activation of protein kinase C (PKC)alpha, whereas lipin-1 overexpression increased PKC alpha phosphorylation. Treatment with PKC alpha inhibitors, like lipin-1 KD, stimulated p21 expression, while lipin-1 overexpression reduced p21 expression, implicating PKC alpha in lipin-1-induced regulation of p21 expression. Taken together, these results suggest that lipin-1-mediated downregulation of p21 is critical for the progress of keratinocyte differentiation after the initial commitment of keratinocytes to differentiation induced by p21, and that PKC alpha is involved in p21 expression regulation by lipin-1.