Tissue substructure-specific deposition of the β3-containing laminin-332 in the biliary epithelium of human and mouse livers
Tissue substructure-specific deposition of the β3-containing laminin-332 in the biliary epithelium of human and mouse livers
复制标题
含β3的层粘连蛋白-332在人和小鼠肝脏胆管上皮中的组织亚结构特异性沉积
DOI：
10.1016/j.bbrc.2020.01.104
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发表时间：
2020
影响因子：
3.1
通讯作者：
Itoh Tohru
中科院分区：
文献类型：
--
作者：
Yamada Minami;Okada Hajime;Kikkawa Yamato;Miyajima Atsushi;Itoh Tohru
层粘连蛋白是一个基底膜蛋白家族，其选择性和时空表达谱与其在不同组织的发育、维持和功能调节中的不同功能有关。在肝脏中，含有α1和α5的层粘连蛋白亚型被证明与胆管上皮组织的发育过程密切相关。然而，其他层粘连蛋白亚型在胆管形成和功能中的可能作用仍不清楚。在这里，我们评估了公共的单细胞RNA测序数据库，以揭示层粘连蛋白基因的表达格局，并发现层粘连蛋白-332亚单位的基因在EpCAM+胆管上皮细胞群中共同表达。β-3和γ-2亚单位基因的表达仅限于肝内胆管上皮细胞，并且它们之间表现出明显的异质性。我们证实了层粘连蛋白-β3在小鼠肝脏中表达的异质性，这与胆管上皮的形态亚结构密切相关。最后，我们建立了肝上皮组织特异性的层粘连蛋白-β3基因敲除小鼠，发现在生理条件下，这个层粘连蛋白亚单位是必不可少的。总之，我们目前的发现已经确定β3亚单位和相关的层粘连蛋白-332亚基是有用的标记和潜在的重要调节分子，对于未来了解肝胆系统的病理生理。
Laminin is a family of basement membrane proteins, whose selective and spatiotemporal expression profiles are linked to their various functions in development, maintenance, and functional regulation of different tissues. In the liver, α1-and α5-containing laminin isoforms have been documented to be critically involved in the developmental process of the epithelial tissue of the bile duct. However, possible roles of other laminin isoforms in bile duct formation and function remain elusive. Here, we evaluated public single-cell RNA sequencing databases on human liver cells to reveal expression landscape of laminin genes, and found that genes for laminin-332 subunits were conjointly expressed in the EPCAM+biliary epithelial cell population. Expression of the β3 and γ2 subunit genes was restricted to biliary epithelial cells in the liver and, remarkably, showed apparent heterogeneity among them. We confirmed the heterogeneous nature of the laminin-β3 expression in murine livers, which was firmly related to morphological substructures in the biliary epithelium. Finally, we generated the liver epithelial tissue-specific laminin- β3 knockout mice and found that this laminin subunit was dispensable under physiological conditions. Together, our present findings have identified the β3 subunit and the related laminin-332 isoform as useful markers and potentially important regulatory molecules for future understanding of pathophysiology in the hepatobiliary system.