1. Single-cell RNA transcriptomic reveal the mechanism of MSC derived small extracellular vesicles against DKD fibrosis.
- Author
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Ji C, Zhang J, Shi H, Chen B, Xu W, Jin J, and Qian H
- 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
- 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
1 + Arg1+ macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+ Col4a5+ /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.1 /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., (© 2024. The Author(s).)- Published
- 2024
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