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| Status |
Public on Apr 07, 2021 |
| Title |
Adenylate kinase 4 Promotes the expression of Inflammatory Genes in Macrophages via Hif-1a |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Macrophages comprise the first line of defense against various pathogens. Classically activated macrophages (M1), induced by IFNg and LPS, express a high level of inflammatory cytokines and contribute to inflammatory processes. By contrast, alternatively activated macrophages (M2) are induced by IL-4/IL-13, produce IL-10, and display anti-inflammatory activity. Adenylate kinase 4 (Αk4), an enzyme that transfers phosphate group among ATP/GTP, AMP, and ADP, is a key modulator of ATP and is involved in maintaining the homeostasis of cellular nucleotides which is essential for the function of cells. However, its role in regulating the function of macrophages is not fully understood. Here we report that the expression of Ak4 is induced in M1 but not M2 macrophages. Suppressing the expression of Ak4 in M1 macrophages with shRNA enhances the production of ATP. RNA-seq analysis identifies several inflammation-related genes, including Il1b, Il6, Tnfa, Nos2 and Hif1a, as downstream targets of Ak4. We further demonstrate that Ak4 and Hif1a form a positive feedback loop in sustaining the expression of the inflammation-related genes. Our data depict a potential mechanism linking energy consumption and inflammation in macrophages.
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| Overall design |
Total M1 macrophages mRNA profile of scramble and Ak4 shRNA KD
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| Contributor(s) |
Miaw |
| Citation(s) |
33790902 |
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| Submission date |
Jan 08, 2020 |
| Last update date |
Apr 07, 2021 |
| Contact name |
Shi-Chuen Miaw |
| E-mail(s) |
smiaw@ntu.edu.tw
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| Phone |
0939676785
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| Organization name |
National Taiwan University, College of Medicine
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| Department |
Immunology
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| Street address |
No.1 Jen Ai road section 1
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| City |
Taipei |
| ZIP/Postal code |
100 |
| Country |
Taiwan |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA599952 |
| SRA |
SRP240358 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE143302_Analysis_Result_version3_20191111.xlsx |
10.3 Mb |
(ftp)(http) |
XLSX |
| GSE143302_Raw_count.txt.gz |
477.7 Kb |
(ftp)(http) |
TXT |
| GSE143302_normalied.txt.gz |
722.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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