Hepatocytes undergo the metaplasia into ductal biliary epithelial cells (BECs) in response to chronic injury, and subsequently contribute to liver regeneration. The mechanism underlying hepatocyte-to-ductal metaplasia has not been explored until now. In mouse models of liver fibrosis, a florid BEC response was observed in fibrotic liver, and the depletion of myofibroblasts attenuated BEC expansion remarkably. Then, in hepatocyte fate-tracing mouse model, we demonstrated the conversion of mature hepatocytes into ductal BECs in fibrotic liver, and the depletion of myofibroblasts diminished the hepatocyte-to-ductal metaplasia. Finally, the mechanism underlying the metaplasia was investigated. Myofibroblasts secreted laminin-rich extracellular matrix, and then laminin induced hepatocyte-to-ductal metaplasia through ɑvβ6 integrin. Therefore, our results demonstrated myofibroblasts induce the conversion of mature hepatocytes into ductal BECs through laminin-ɑvβ6 integrin, which reveals that the strategy improve regeneration in fibrotic liver through the modification of specific microenvironment.

肝细胞在对慢性损伤的反应中经历化生为导管胆管上皮细胞（BEC），并随后促进肝脏再生。迄今为止，尚未探索肝细胞向导管化生的潜在机制。在肝纤维化的小鼠模型中，在纤维化肝脏中观察到了微弱的BEC反应，并且成肌纤维细胞的耗竭显着减弱了BEC的扩增。然后，在追踪肝细胞命运的小鼠模型中，我们证明了成熟肝细胞在纤维化肝中转化为导管BEC，而成肌纤维细胞的耗竭减少了肝细胞至导管的化生。最后，研究了化生的潜在机制。肌成纤维细胞分泌富含层粘连蛋白的细胞外基质，然后通过ɑvβ6整合素诱导层粘连蛋白诱导肝细胞-导管化生。因此，