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PERK is essential for proliferation of intestinal stem cells in mice

PERK is essential for proliferation of intestinal stem cells in mice

Authors :
Xinlin Wu
Zhihao Liu
Jinli Liao
Jia Xu
Hong Zhan
Hongyan Wei
Jingjing Liu
Zhen Yang
Source :
Experimental Cell Research. 375:42-51
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

Protein kinase RNA-like Endoplasmic Reticulum Kinase (PERK) is an endoplasmic reticulum stress sensor that possesses pro-survival capability and contributes to cell homeostasis and survival. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) has been recognized as a stem cell marker in intestinal epithelial cells. To determine whether PERK modulates the proliferation of intestinal stem cells, we investigated the effects of PERK knock-down on intestinal Lgr5-positive stem cells in mice. Lgr5-EGFP knock-in mice were fed with lentivirus-PERK shRNA twice a day for three days. Isolated intestinal Lgr5-positive stem cells were treated with lentivirus-PERK shRNA. The number of Lgr5-positive cells, the proliferation and apoptotic indices, several biomarkers for proliferation and differentiation, and Akt expression in intestinal stem cells were detected in vivo, in vitro and in two intestinal epithelial injury models caused by radiotherapy and sepsis. PERK knock-down could significantly diminish the number and proliferation of Lgr5-positive cells, induce the low expression of several proliferation markers and the high expression of several differentiation markers in Lgr5-positive cells, enhance the apoptotic Lgr5-positive cells, and reduce the Akt expression in intestinal Lgr5-positive stem cells. Similar results were observed in radiotherapy- and sepsis-induced intestinal injuries. Moreover, PERK inhibition markedly decreased the survival of mice in response to radiation and sepsis. These results suggest a critical role for PERK in the proliferation and survival of intestinal stem cells in mice.

Details

ISSN :
00144827
Volume :
375
Database :
OpenAIRE
Journal :
Experimental Cell Research
Accession number :
edsair.doi.dedup.....71d0cf1ad3f2482ededccb883b86beb6
Full Text :
https://doi.org/10.1016/j.yexcr.2018.12.009