Abstract:
: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.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Xu T,Lu Z,Xiao Z,Liu F,Chen Y,Wang Z,Zhu S,Song Ydoi
10.1038/s41419-020-2372-9subject
Has Abstractpub_date
2020-03-23 00:00:00pages
199issue
3issn
2041-4889pii
10.1038/s41419-020-2372-9journal_volume
11pub_type
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