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Senescence suppressed proliferation of host hepatocytes is precondition for liver repopulation.
Biochem Biophys Res Commun 2019; 516(2):591-598BB

Abstract

In the fumarylacetoacetate hydrolase deficient (Fah-/-) mouse, massive liver repopulation can be easily obtained after transplanted hepatocytes. Understanding the mechanisms of complete liver repopulation in Fah-/- mice will be useful for future clinical application. Here, we found that the endogenous hepatocytes in liver of Fah-/- mice undertook senescence during the time of tyrosinemia symptoms. Increase of senescent hepatocytes in Fah-/- mice provided proliferative advantage to the transplanted hepatocytes. Importantly, senescent hepatocytes upregulated the expression of extracellular matrix enzyme, contributing to degradation of extracellular matrix components and weakness of cell adhesion and connection. The liver exhibiting a loose architecture provided the space for the engraftment and expansion of transplanted hepatocytes. These findings underscore the underlying mechanisms of completed liver repopulation in Fah-/- mice. Senescence followed by loose hepatic parenchyma is a preconditioning for liver repopulation, which would be a promising strategy to achieve therapeutic liver repopulation in clinical settings.

Authors+Show Affiliations

Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, 200433, PR China.Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, 200433, PR China.Organ Transplantation Center, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, PR China.Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, 200433, PR China.Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, 200433, PR China.Estern Hepatobilliary Surgery Hospital, Second Military Medical University, Shanghai, 200433, PR China.Organ Transplantation Center, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, PR China.Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, 200433, PR China.Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, 200433, PR China. Electronic address: yphu@smmu.edu.cn.Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai, 200433, PR China. Electronic address: twinkky@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31239154

Citation

Chen, Jiajia, et al. "Senescence Suppressed Proliferation of Host Hepatocytes Is Precondition for Liver Repopulation." Biochemical and Biophysical Research Communications, vol. 516, no. 2, 2019, pp. 591-598.
Chen J, Yang T, Song S, et al. Senescence suppressed proliferation of host hepatocytes is precondition for liver repopulation. Biochem Biophys Res Commun. 2019;516(2):591-598.
Chen, J., Yang, T., Song, S., Liu, Q., Sun, Y., Zhao, L., ... Chen, F. (2019). Senescence suppressed proliferation of host hepatocytes is precondition for liver repopulation. Biochemical and Biophysical Research Communications, 516(2), pp. 591-598. doi:10.1016/j.bbrc.2019.06.103.
Chen J, et al. Senescence Suppressed Proliferation of Host Hepatocytes Is Precondition for Liver Repopulation. Biochem Biophys Res Commun. 2019 Aug 20;516(2):591-598. PubMed PMID: 31239154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Senescence suppressed proliferation of host hepatocytes is precondition for liver repopulation. AU - Chen,Jiajia, AU - Yang,Tao, AU - Song,Shaohua, AU - Liu,Qinggui, AU - Sun,Yu, AU - Zhao,Linghao, AU - Fu,Zhiren, AU - Wang,Min-Jun, AU - Hu,Yi-Ping, AU - Chen,Fei, Y1 - 2019/06/22/ PY - 2019/06/12/received PY - 2019/06/18/accepted PY - 2019/6/27/pubmed PY - 2019/6/27/medline PY - 2019/6/27/entrez KW - Cell transplantation KW - Extracellular matrix KW - Hepatocyte senescence KW - Liver repopulation KW - Proliferative precondition SP - 591 EP - 598 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 516 IS - 2 N2 - In the fumarylacetoacetate hydrolase deficient (Fah-/-) mouse, massive liver repopulation can be easily obtained after transplanted hepatocytes. Understanding the mechanisms of complete liver repopulation in Fah-/- mice will be useful for future clinical application. Here, we found that the endogenous hepatocytes in liver of Fah-/- mice undertook senescence during the time of tyrosinemia symptoms. Increase of senescent hepatocytes in Fah-/- mice provided proliferative advantage to the transplanted hepatocytes. Importantly, senescent hepatocytes upregulated the expression of extracellular matrix enzyme, contributing to degradation of extracellular matrix components and weakness of cell adhesion and connection. The liver exhibiting a loose architecture provided the space for the engraftment and expansion of transplanted hepatocytes. These findings underscore the underlying mechanisms of completed liver repopulation in Fah-/- mice. Senescence followed by loose hepatic parenchyma is a preconditioning for liver repopulation, which would be a promising strategy to achieve therapeutic liver repopulation in clinical settings. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/31239154/Senescence_suppressed_proliferation_of_host_hepatocytes_is_precondition_for_liver_repopulation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(19)31239-2 DB - PRIME DP - Unbound Medicine ER -