Research Paper Volume 9, Issue 5 pp 1359—1374
Aging-associated oxidative stress inhibits liver progenitor cell activation in mice
- 1 Shanghai Institute of Immunology and Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 2 Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 3 Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Received: April 1, 2017 Accepted: April 23, 2017 Published: April 29, 2017
https://doi.org/10.18632/aging.101232How to Cite
Copyright: Cheng et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Recent studies have discovered aging-associated changes of adult stem cells in various tissues and organs, which potentially contribute to the organismal aging. However, aging-associated changes of liver progenitor cells (LPCs) remain elusive. Employing young (2-month-old) and old (24-month-old) mice, we found diverse novel alterations in LPC activation during aging. LPCs in young mice could be activated and proliferate upon liver injury, whereas the counterparts in old mice failed to respond and proliferate, leading to the impaired liver regeneration. Surprisingly, isolated LPCs from young and old mice did not exhibit significant difference in their clonogenic and proliferative capacity. Later, we uncovered that the decreased activation and proliferation of LPCs were due to excessive reactive oxygen species produced by neutrophils infiltrated into niche, which was resulted from chemokine production from activated hepatic stellate cells during aging. This study demonstrates aging-associated changes in LPC activation and reveals critical roles for the stem cell niche, including neutrophils and hepatic stellate cells, in the negative regulation of LPCs during aging.
Abbreviations
LPCs: liver progenitor cells; ROS: reactive oxygen species; AFP: α-fetoprotein; CK19: cytokeratin 19; EpCAM: epithelial cell adhesion molecule; MDA: malondialdehyde; CDE diet: choline-deficient, ethionine-supplemented diet; ECM: extracellular matrix.