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.
|
Authors | Ting Xu, Zhiwen Lu, Zhuanglong Xiao, Fang Liu, Yuhua Chen, Zhijun Wang, Shenghua Zhu, Yuhu Song |
Journal | Cell death & disease
(Cell Death Dis)
Vol. 11
Issue 3
Pg. 199
(03 23 2020)
ISSN: 2041-4889 [Electronic] England |
PMID | 32251270
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antigens, Neoplasm
- Integrins
- Laminin
- integrin alphavbeta6
|
Topics |
- Animals
- Antigens, Neoplasm
(metabolism)
- Cell Proliferation
- Disease Models, Animal
- Humans
- Integrins
(metabolism)
- Laminin
(metabolism)
- Liver Cirrhosis
(physiopathology)
- Mice
- Myofibroblasts
(metabolism)
- Transfection
|