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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
- 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.
- Subjects :
- 0301 basic medicine
endocrine system
Cell
Apoptosis
Biology
Endoplasmic Reticulum
Stem cell marker
Receptors, G-Protein-Coupled
Small hairpin RNA
Mice
eIF-2 Kinase
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Cell Lineage
Intestinal Mucosa
Protein kinase B
Cell Proliferation
Stem Cells
Endoplasmic reticulum
Lentivirus
LGR5
Cell Differentiation
Epithelial Cells
Cell Biology
Intestines
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
Stem cell
Subjects
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