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| Status |
Public on May 01, 2024 |
| Title |
PFKFB3 drives renal fibrosis through promoting histone lactylation-mediated NF-đťś…B activation [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease. However, the underlying mechanism remains largely unclear. Here, we observed that PFKFB3, a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells following ischemia-reperfusion injury in mice, as well as in multiple etiologies of chronic kidney disease patients. Proximal tubular epithelial-specific deletion of PFKFB3 significantly reduced renal lactate levels, mitigated inflammation and fibrosis, and preserved renal function in the IRI mouse model. To explore the mechanism of PFKFB3 in renal fibrosis, we performed RNA-sequencing (RNA-seq) on the kidney cortices from IRI mice. Of note, we found that PFKFB3-mediated kidney tubular glycolytic reprogramming markedly enhanced H4K12la lactylation. To further explore the potential functional significance of H4K12la in renal fibrosis, we performed genome-wide cleavage under targets and tagmentation (CUT&Tag) analysis to identify candidate genes regulated by H4K12la in sham and IRI kidney. Following CUT&Tag, H4K12la-associated DNAs were amplified using non-biased conditions, labeled, and sequenced with Illumina NovaSeq 6000.
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| Overall design |
To investigate the role of PFKFB3 in the renal fibrosis, proximal tubular cell conditional Pfkfb3 knockout mice and their littermate controls were used and followed by ischemia kidney injury . Total RNA isolated from IRI kidney tissues was used as input material for the RNA sequence.
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| Contributor(s) |
Wang Y, Li H, Chen W, Liu Q, Mao H |
| Citation missing |
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| BioProject |
PRJNA1105920 |
| Submission date |
Apr 30, 2024 |
| Last update date |
May 02, 2024 |
| Contact name |
yating wang |
| E-mail(s) |
wangyt73@mail.sysu.edu.cn
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| Phone |
15920488562
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| Organization name |
The First Affiliated Hospital, Sun Yat-sen University
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| Department |
Department of Nephrology
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| Lab |
NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology
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| Street address |
58th Zhongshan Road II The First Affiliated Hospital ,Sun Yat-Sen University
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510080 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| GSM8242994 |
Pfkfb3WT1, Kidney, IRI day14 |
| GSM8242995 |
Pfkfb3WT2, Kidney, IRI day14 |
| GSM8242996 |
Pfkfb3WT3, Kidney, IRI day14 |
| GSM8242997 |
Pfkfb3ΔPTC1, Kidney, IRI day14 |
| GSM8242998 |
Pfkfb3ΔPTC2, Kidney, IRI day14 |
| GSM8242999 |
Pfkfb3ΔPTC3, Kidney, IRI day14 |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE266242_IRI_kidney_Count_matrix.xls.gz |
546.6 Kb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
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