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Series GSE118732 Query DataSets for GSE118732
Status Public on Aug 20, 2018
Title Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptomes of Colon Epithelial Cell from Wild Type and Pkm2-/- mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Purpose: PKM2-mediated metabolic switch to aerobic glycolysis plays a critical role in promoting cell survival and proliferation. However, little is known about the function of intestinal epithelial PKM2 in intestinal homeostasis. Here we investigated whether and how intestinal epithelial PKM2 modulates the morphology and function of the adult intestine in experimental murine colitis.

Methods: Colonoscopic biopsies from the Crohn’s disease (CD) and ulcerative colitis (UC) patients (10 each) were analyzed for PKM2 expression. We also generated intestinal epithelial-specific Pkm2 knockout mice and employed them to examine PKM2 function. Mouse intestinal inflammation was induced with dextran sulfate sodium (DSS) in drinking water. Disease phenotypes were investigated by mouse survival, body weight, colon length and analysis of immune cell infiltration in colon, intestinal epithelial cell gene profiling and signal pathway.

Results: Intestinal epithelial PKM2 level in UC and CD patients was significantly decreased compared to that from non-inflamed intestinal epithelium. Similar reduction of intestinal epithelial PKM2 was observed in mice with experimental colitis. Supporting the notion that PKM2 serves as a safeguard against colitis, intestinal epithelial-specific Pkm2-deficient (Pkm2-/-) mice displayed a severer intestinal inflammation, companying with shortened colon, disruption of epithelial tight junction, higher permeability, elevation of inflammatory cytokines and immune cell infiltration, compared with wild-type mice. Gene profiling and western blot analysis indicated that cell survival signaling, particularly the Akt/β-catenin pathways, were downregulated in Pkm2-/- mice. Functional assay using mouse primary colonic epithelial cells confirmed that Pkm2 reduction decreased proliferation and migration of epithelial cells, while enhanced expression of Pkm2 was associated with increased transcriptional activity of β-catenin. Moreover, increasing mouse intestinal epithelial Pkm2 expression via delivery of Pkm2-expressing plasmid attenuated DSS-induced experimental colitis.

Conclusions: Intestinal epithelial PKM2, through activating Wnt/β-catenin signaling, induces a strong proliferative and migratory response that increases cell survival and wound healing under colitic condition.
Overall design mRNA profiles of colon epithelial cell from Wild Type and Pkm2-/- mice treated with 2.5% DSS for 3 days were generated by Illumina Hiseq X Ten platform
Contributor(s) Liang H, Zen K
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Submission date Aug 19, 2018
Last update date Mar 01, 2019
Contact name HONGWEI LIANG
Organization name Nanjing University
Street address Qixia District, Xianlin Road No.163
City Nanjing
State/province Jiangsu Province
ZIP/Postal code 210023
Country China
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (2)
GSM3344697 WT-3D
GSM3344698 Pkm2-/- 3D
BioProject PRJNA486652
SRA SRP158324

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE118732_RAW.tar 980.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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