Molecular mechanisms regulating epithelial morphogenesis during the development of bile ducts

我们发现含有α1的层粘连蛋白调节了胆管细胞的谱系决定和胆管形态发生的初始阶段，而含有α5的层粘连蛋白则有助于成熟胆管结构的形成。我们还搜索了成熟胆管细胞中上调的基因，并确定了转录因子Grhl2 （granyhead like 2）。我们将Grhl2引入肝祖细胞系HPPL，发现Grhl2使囊肿中央管腔增大。我们进一步发现Grhl2增强了HPPL单层的屏障功能，上调了Claudin3、Claudin4和Rab25的表达。因此，我们得出结论，Grhl2通过调控Clandin3、Claudin4和Rab253之间的分子网络促进上皮管腔成熟。

We revealed that α1-containing laminin regulated the lineage determination of cholangiocytes and the initial stage of bile duct morphogenesis, whereas α5-containing laminin contributes to the formation of mature duct structures. We also searched genes upregulated in mature cholangiocytes and identified a transcription factor grainyhead like 2(Grhl2). We introduced Grhl2 into HPPL, a liver progenitor cell line, and found that Grhl2 enlarged the central lumen of cysts. We further found that Grhl2 enhanced barrier function of the monolayer of HPPL and upregulated expression of Claudin3, Claudin4, and Rab25. Thus, we conclude that Grhl2 promotes the maturation of epithelial lumen by governing the molecular network among Clandin3, Claudin4, and Rab253.