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Single-cell RNA transcriptomic reveal the mechanism of MSC derived small extracellular vesicles against DKD fibrosis.
- Source :
-
Journal of nanobiotechnology [J Nanobiotechnology] 2024 Jun 18; Vol. 22 (1), pp. 339. Date of Electronic Publication: 2024 Jun 18. - Publication Year :
- 2024
-
Abstract
- Diabetic kidney disease (DKD), a chronic kidney disease, is characterized by progressive fibrosis caused due to persistent hyperglycemia. The development of fibrosis in DKD determines the patient prognosis, but no particularly effective treatment. Here, small extracellular vesicles derived from mesenchymal stem cells (MSC-sEV) have been used to treat DKD fibrosis. Single-cell RNA sequencing was used to analyze 27,424 cells of the kidney, we have found that a novel fibrosis-associated TGF-β <subscript>1</subscript> <superscript>+</superscript> Arg1 <superscript>+</superscript> macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin <superscript>+</superscript> Col4a5 <superscript>+</superscript> mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-β <subscript>1</subscript> /Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates renal fibrosis niche. Subsequently, the transcriptome sequencing and LC-MS/MS analysis indicated that MSC-sEV intervention could restore the levels of the kinase ubiquitin system in DKD and attenuate renal interstitial fibrosis via delivering CK1δ/β-TRCP to mediate YAP ubiquitination degradation in mesangial cells. Our findings demonstrate the unique cellular and molecular mechanisms of MSC-sEV in treating the DKD fibrosis niche at a single-cell level and provide a novel therapeutic strategy for renal fibrosis.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Male
Mice, Inbred C57BL
Humans
Macrophages metabolism
Signal Transduction
Transforming Growth Factor beta1 metabolism
Mesangial Cells metabolism
Kidney pathology
Kidney metabolism
Extracellular Vesicles metabolism
Fibrosis
Mesenchymal Stem Cells metabolism
Single-Cell Analysis
Diabetic Nephropathies metabolism
Diabetic Nephropathies therapy
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 1477-3155
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of nanobiotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 38890734
- Full Text :
- https://doi.org/10.1186/s12951-024-02613-2