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| Status |
Public on Jun 26, 2024 |
| Title |
Integrin αM promotes macrophage alternative M2 polarization in hyperuricemia-related chronic kidney disease |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney diseases. Here, we aim to investigate whether and how macrophage integrin αM (ITGAM) contributes to hyperuricemia-related CKD. In vivo, we explored dynamic characteristics of renal tissue in C57BL/6J mice with hyperuricemia-related CKD. By incorporating transcriptomics and phosphoproteomics data, we analyzed gene expression profile, hub genes and potential pathways. In vitro, we validated bioinformatic findings under different conditions with interventions corresponding to core nodes. We found that hyperuricemia-related CKD was characterized by elevated serum uric acid levels, impaired renal function, activation of macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed Itgam as the potential core gene and was associated with focal adhesion signaling. Notably, we confirmed the upregulated expression of macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys. In vitro, through silencing Itgam, inhibiting p-FAK or p-AKT1 phosphorylation, and concurrent inhibiting of p-FAK while activating p-AKT1 all contributed to the modulation of macrophage M2 polarization. Our results indicated targeting macrophage ITGAM might be a promising therapeutic approach for preventing CKD.
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| Overall design |
Seven-week male mice (C57BL/6J, 22-25g) were purchased from Dossy Experimental Animal Co., Ltd (Chengdu, China). These mice were maintained in the controlled environment for 1 week (temperature at 20 ± 2 ℃, humidity at 50–60%, and 12-hour light/dark cycle) and provided with food and water ad libitum. To study dynamic characteristic of uric acid-induced kidney injury, we randomly divided mice into 4 groups: day 0, day 7, day 14, and day 21 groups (n=6 per group). The mice in group day 7, 14 and 21 were administered with a mixture of adenine (0.16 g/kg) and potassium oxonate (2.4 g/kg) by oral gavage once daily.Finally, kidney tissue from day 0 (Control) and day 21 groups were performed mRNA sequencing.
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| Contributor(s) |
Liu J, Guo F, Ma L, Fu P |
| Citation(s) |
38911067 |
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| Submission date |
Mar 28, 2024 |
| Last update date |
Jun 26, 2024 |
| Contact name |
Jing Liu |
| E-mail(s) |
liujinghx@gmail.com
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| Phone |
15102837860
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| Organization name |
West China Hospital of Sichuan University
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| Street address |
No.17, Renmin South Rd 3rd Section
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| City |
Chengdu |
| State/province |
Sichuan SC |
| ZIP/Postal code |
610041 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1092994 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE262687_count_data.txt.gz |
407.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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