Journal
HEPATOLOGY
Volume 70, Issue 6, Pages 2092-2106Publisher
WILEY
DOI: 10.1002/hep.30790
Keywords
-
Categories
Funding
- National Key Basic Research Program of China [2015CB942800]
- National Natural Science Foundation of China [31730060, 31801214, 91539201]
- National Key Research and Development Program of China [2017YFA0106600]
- Natural Science Foundation Project of Chongqing [cstc2014jcyjA10088]
- Fundamental Research Funds for the Central Universities [XDJK2017A007, XDJK2015B011]
- 111 Program [B14037]
Ask authors/readers for more resources
The liver has a high regenerative capacity. Upon two-thirds partial hepatectomy, the hepatocytes proliferate and contribute to liver regeneration. After severe liver injury, when the proliferation of residual hepatocytes is blocked, the biliary epithelial cells (BECs) lose their morphology and express hepatoblast and endoderm markers, dedifferentiate into bipotential progenitor cells (BP-PCs), then proliferate and redifferentiate into mature hepatocytes. Little is known about the mechanisms involved in the formation of BP-PCs after extreme liver injury. Using a zebrafish liver extreme injury model, we found that mammalian target of rapamycin complex 1 (mTORC1) signaling regulated dedifferentiation of BECs and proliferation of BP-PCs. mTORC1 signaling was up-regulated in BECs during extreme hepatocyte ablation and continuously expressed in later liver regeneration. Inhibition of mTORC1 by early chemical treatment before hepatocyte ablation blocked the dedifferentiation from BECs into BP-PCs. Late mTORC1 inhibition after liver injury reduced the proliferation of BP-PC-derived hepatocytes and BECs but did not affect BP-PC redifferentiation. mTOR and raptor mutants exhibited defects in BEC transdifferentiation including dedifferentiation, BP-PC proliferation, and redifferentiation, similar to the chemical inhibition. Conclusion: mTORC1 signaling governs BEC-driven liver regeneration by regulating the dedifferentiation of BECs and the proliferation of BP-PC-derived hepatocytes and BECs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available