Single cell multi-omics of fibrotic kidney reveal epigenetic regulation of antioxidation and apoptosis within proximal tubule
Background Until now, there has been no particularly effective treatment for chronic kidney disease (CKD). Fibrosis is a common pathological change that exist in CKD. Methods To better understand the transcriptional dynamics in fibrotic kidney, we make use of single-nucleus assay for transposase-acc...
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Published in | Cellular and molecular life sciences : CMLS Vol. 81; no. 1; p. 56 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cham
Springer International Publishing
01.12.2024
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Background
Until now, there has been no particularly effective treatment for chronic kidney disease (CKD). Fibrosis is a common pathological change that exist in CKD.
Methods
To better understand the transcriptional dynamics in fibrotic kidney, we make use of single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and single-cell RNA sequencing (scRNA-seq) from GEO datasets and perform scRNA-seq of human biopsy to seek possible transcription factors (TFs) regulating target genes in the progress of kidney fibrosis across mouse and human kidneys.
Results
Our analysis has displayed chromatin accessibility, gene expression pattern and cell–cell communications at single-cell level in kidneys suffering from unilateral ureteral obstruction (UUO) or chronic interstitial nephritis (CIN). Using multimodal data, there exists epigenetic regulation producing less Sod1 and Sod2 mRNA within the proximal tubule which is hard to withstand oxidative stress during fibrosis. Meanwhile, a transcription factor Nfix promoting the apoptosis-related gene Ifi27 expression found by multimodal data was validated by an in vitro study. And the gene Ifi27 upregulated by in situ AAV injection within the kidney cortex aggravates kidney fibrosis.
Conclusions
In conclusion, as we know oxidation and apoptosis are traumatic factors during fibrosis, thus enhancing antioxidation and inhibiting the Nfix-Ifi27 pathway to inhibit apoptosis could be a potential treatment for kidney fibrosis. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1420-682X 1420-9071 |
DOI: | 10.1007/s00018-024-05118-1 |