Single-cell RNA transcriptomic reveal the mechanism of MSC derived small extracellular vesicles against DKD fibrosis
Cheng Ji, Jiahui Zhang, Hui Shi, Binghai Chen, Wenrong Xu, Jianhua Jin, Hui Qian
TL;DR
This study uses single-cell RNA sequencing to uncover how MSC-derived extracellular vesicles combat kidney fibrosis in diabetic patients.
Contribution
The paper identifies a novel fibrosis-associated macrophage subpopulation and reveals how MSC-sEVs restore kinase ubiquitin systems to reduce fibrosis.
Findings
A TGF-β1+Arg1+ macrophage subpopulation expands in DKD and promotes fibrosis.
MSC-sEVs deliver CK1δ/β-TRCP to mediate YAP ubiquitination and reduce mesangial fibrosis.
MSC-sEV intervention attenuates renal interstitial fibrosis by restoring kinase ubiquitin systems.
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-β1+Arg1+ macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+Col4a5+ mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-β1/Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates…
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Taxonomy
TopicsIslamic Finance and Banking Studies · Microfinance and Financial Inclusion