Galectin-7 Regulates Keratinocyte Proliferation and Differentiation through JNK-miR-203-p63 Signaling.
Galectin-7 Regulates Keratinocyte Proliferation and Differentiation through JNK-miR-203-p63 Signaling.
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DOI：
10.1038/jid.2015.366
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Liu FT
中科院分区：
文献类型：
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作者：
Chen HL;Chiang PC;Lo CH;Lo YH;Hsu DK;Chen HY;Liu FT
Galectin-7是β-半乳糖苷结合蛋白家族的一员，主要在包括角质形成细胞在内的复层上皮细胞中表达。文献中有信息表明该蛋白在角质形成细胞的生存和生长调节中起作用，但其潜在的机制仍相对不清楚。此外，它在表皮中的表达模式表明，它也参与了角质形成细胞分化的调节。在这里，我们证明了Galectin-7基因敲除导致角质形成细胞分化减少和增殖增加。利用芯片和深度测序分析，我们发现Galectin-7分别正向和负向调节microRNA(MiR)-203和miR-146a的表达。我们发现Galectin-7通过miR-203而不是miR-146a调节角质形成细胞的分化和增殖。在角质形成细胞中，Galectin-7或miR-203的敲除会增加p63的表达，p63是一种参与皮肤发育的必要转录因子。在Galectin-7基因敲除模型中挽救miR-203的表达使p63的表达降低到基线水平。Galectin-7的表达增加上调了c-jun氨基末端激酶(JNK)的蛋白水平，这是miR-203表达所必需的。最后，我们证实Galectin-7可以与JNK1结合并保护其免受泛素化和降解。因此，我们的数据提示Galectin-7的细胞内功能：通过JNK1-miR-203-p63途径调节角质形成细胞的增殖和分化。
Galectin-7, a member of the β-galactoside-binding protein family, is primarily expressed in stratified epithelial cells, including keratinocytes. There is information in the literature suggesting a role for this protein in regulation of keratinocyte survival and growth, but the underlying mechanism remains relatively unknown. Moreover, its expression pattern in the epidermis suggests that it is also involved in the regulation of keratinocyte differentiation. Here, we demonstrate that galectin-7 knockdown results in reduced differentiation and increased proliferation of keratinocytes. Using microarray and deep-sequencing analyses, we found that galectin-7 positively and negatively regulates microRNA (miR)-203 and miR-146a expression, respectively. We show that galectin-7 regulates keratinocyte differentiation and proliferation through miR-203 but not miR-146a. A knockdown of either galectin-7 or miR-203 in keratinocytes increases expression of p63, an essential transcription factor involved in skin development. Rescue of miR-203 expression in a galectin-7 knockdown model reduces p63 expression to baseline. Increased galectin-7 expression up-regulates c-Jun N-terminal kinase (JNK) protein levels, which is required for miR-203 expression. Finally, we establish that galectin-7 can be associated with JNK1 and protect it from ubiquitination and degradation. Thus, our data suggest an intracellular function of galectin-7: regulation of keratinocyte proliferation and differentiation through the JNK1-miR-203-p63 pathway.