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| Status |
Public on Nov 01, 2023 |
| Title |
Hypermethylation suppresses microRNA-219a-2 to activate the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis [RRBS] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Epigenetic regulations, such as DNA methylation and microRNAs, play an important role in renal fibrosis. Here, we report the regulation of microRNA-219a-2 (mir-219a-2) by DNA methylation in fibrotic kidneys, unveiling the crosstalk between these epigenetic mechanisms. Through genome-wide DNA methylation analysis and pyro-sequencing, we detected the hypermethylation of mir-219a-2 in renal fibrosis induced by unilateral ureter obstruction (UUO) or renal ischemia/reperfusion, which was accompanied by a significant decrease in mir-219a-5p expression. Functionally, overexpression of mir-219a-2 enhanced fibronectin induction during hypoxia or TGF-b1 treatment of cultured renal cells. In mice, inhibition of mir-219a-5p suppressed fibronectin accumulation in UUO kidneys. ALDH1L2 was identified to be the direct target gene of mir-219a-5p in renal fibrosis. Mir-219a-5p suppressed ALDH1L2 expression in cultured renal cells, while inhibition of mir-219a-5p prevented the decrease of ALDH1L2 in UUO kidneys. Knockdown of ALDH1L2 enhanced PAI-1 induction during TGF-b1 treatment of renal cells, which was associated with fibronectin expression. In conclusion, the hypermethylation of mir-219a-2 in response to fibrotic stress attenuates mir-219a-5p expression and induces the up-regulation of its target gene ALDH1L2, which may reduce fibronectin deposition by suppressing PAI-1.
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| Overall design |
To investigate the differentially methylated genes in kidney fibrosis, C57BL/6 mice were subjected to unilateral ureter obstruction for 7 days (UUO7D), bilateral kidney ischemia 25 minutes and 1 week reperfusion, bilateral kidney ischemia 25 minutes and 1 month reperfusion, or sham operation. The genomic DNA from the kidney cortex and outer medulla were extracted for bisulfite sequencing.
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| Contributor(s) |
Wei Q, Xiao X, Shi H, Dong Z |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jun 28, 2023 |
| Last update date |
Nov 01, 2023 |
| Contact name |
Qingqing Wei |
| E-mail(s) |
QWEI@AUGUSTA.EDU
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| Phone |
7067213551
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| Organization name |
Augusta University
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| Department |
Cellular Biology & Anatomy
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| Lab |
CB1124
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| Street address |
1460 Laney Walker Blvd.
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| City |
AUGUSTA |
| State/province |
Georgia |
| ZIP/Postal code |
30912 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (8)
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| GSM7516857 |
mouse kidney, bilateral kidney ischemia 25 minutes and 1 month reperfusion |
| GSM7516858 |
mouse kidney, bilateral kidney ischemia 25 minutes and 1 week reperfusion |
| GSM7516859 |
mouse kidney, sham for kidney ischemia/reperfusion |
| GSM7516860 |
mouse kidney, UUO7D, 5AZA, sample 1 |
| GSM7516861 |
mouse kidney, UUO7D, 5AZA, sample 2 |
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| This SubSeries is part of SuperSeries: |
| GSE236019 |
Hypermethylation suppresses microRNA-219a-2 to activate the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis |
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| Relations |
| BioProject |
PRJNA988441 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE236018_RAW.tar |
105.5 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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