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| Status |
Public on Dec 07, 2020 |
| Title |
IGF2R-initiated Proton Rechanneling Dictates an Anti-inflammatory Property in Macrophages |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Metabolic trait in macrophages can be rewired by insulin like growth factor 2 (IGF2), however, how IGF2 modulates the cellular dynamics and functionality remains unclear. We demonstrate here that IGF2 exhibits dual and opposing roles in controlling inflammatory phenotypes in macrophages via regulating glucose metabolism. Such difference relies on the dominant activation of IGF2R by low dose IGF2 and IGF1R by high dose IGF2. IGF2R activation leads to proton rechanneling to the mitochondrial intermembrane space, and enables sustained oxidative phosphorylation. Mechanistically,low dose IGF2 induces nucleus translocation of IGF2R that promotes Dnmt3a-mediated DNA methylation via activating GSK3β, and subsequently impairs the expression ofvacuolar-type H+-ATPase (v-ATPase).This sequestrated assembly of v-ATPase inhibits the channeling of protons to lysosomes and leads to their rechanneling to mitochondria. An IGF2R-specific IGF2 mutant only induces anti-inflammatory response and inhibits colitis progression. Altogether, our findings highlight a novel role of IGF2R activation in dictating anti-inflammatory macrophages.
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| Overall design |
Three samples of IGF2-preprogrammed peritoneal macrophages were analyzed by genome-wide methylation sequencing
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| Contributor(s) |
Wang X, Shi Y, Wang Y |
| Citation(s) |
33239287 |
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| Submission date |
May 28, 2020 |
| Last update date |
Dec 07, 2020 |
| Contact name |
Xuefeng Wang |
| E-mail(s) |
wangxuefeng@sibs.ac.cn
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| Organization name |
Chinese Academy of Sciences
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| Street address |
320 Yueyang Road
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| City |
Shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (1) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA635686 |
| SRA |
SRP265159 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE151404_RAW.tar |
107.1 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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