α1- and α5-containing Laminins Regulate the Development of Bile Ducts via β1 Integrin Signals

摘要: Signals derived from basal lamina components are important for developing three-dimensional architecture of epithelial tissues. Laminins consisting α, β, and γ subunits in play pivotal roles the formation maintenance tissue structures. However, it remains unclear which laminin isoforms transmit signals how cells receive them to regulate multiple developmental processes. In culture a liver progenitor cell line, Hepatic Progenitor Cells Proliferating on Laminin (HPPL), establish apicobasal polarity form cysts with central lumen. Neutralizing antibody against β1 integrin blocked cyst structure, indicating that signaling was necessary throughout morphogenesis. Although addition α1-containing laminin, ligand integrin, induced formation, dispensable cyst, suggesting HPPL produces another maintain structure. Indeed, we found produced α5-containing siRNA α5 partially inhibited lumen formation. fetal liver, p75NTR+ periportal fibroblasts bile duct cells, known as cholangiocytes, expressed α1- laminins, respectively. KO cholangiocytes normally emerged, but number ducts decreased. These results suggest is sufficient component commitment bipotential progenitors polarization, whereas mature Thus, laminins differentially sequential events tissues via signals.