Aging-associated oxidative stress inhibits liver progenitor cell activation in mice.
Aging-associated oxidative stress inhibits liver progenitor cell activation in mice.
复制标题
衰老相关的氧化应激抑制小鼠肝脏祖细胞活化
DOI：
10.18632/aging.101232
复制
发表时间：
2017-04-29
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Cheng Y;Wang X;Wang B;Zhou H;Dang S;Shi Y;Hao L;Luo Q;Jin M;Zhou Q;Zhang Y
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.
