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Exosome-mediated pyroptosis of miR-93-TXNIP-NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis-induced acute kidney injury |
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| Authors: | Chen-Xia Juan Yan Mao Qian Cao Yan Chen Lan-Bo Zhou Sheng Li Hao Chen Jia-He Chen Guo-Ping Zhou Rui Jin |
| Affiliation: | 1. Department of Pediatrics, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China Department of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China Contribution: Conceptualization (lead), Formal analysis (lead), Investigation (lead), Methodology (lead), Software (equal), Supervision (equal), Validation (lead), Visualization (lead), Writing - original draft (lead);2. Department of Pediatrics, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China Contribution: Conceptualization (supporting), Data curation (lead), Formal analysis (supporting), Writing - review & editing (lead);3. Department of Pediatrics, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China Contribution: Data curation (supporting), Investigation (supporting), Methodology (lead), Project administration (supporting), Software (supporting);4. Department of Nephrology, Affiliated Geriatric Hospital, Nanjing Medical University, Nanjing, China Contribution: Methodology (supporting), Resources (lead), Supervision (supporting);5. Department of Dermatology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China Contribution: Validation (supporting), Visualization (supporting), Writing - review & editing (supporting);6. Department of Pediatrics, Yancheng Maternity and Child Health Care Hospital, Yancheng, China Contribution: Data curation (supporting), Formal analysis (supporting), Resources (supporting), Software (supporting), Writing - review & editing (supporting);7. Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China Contribution: Investigation (supporting), Project administration (supporting);8. Department of Pediatrics, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China |
| Abstract: | Sepsis is a systemic inflammatory response syndrome caused by infection, resulting in organ dysfunction. Sepsis-induced acute kidney injury (AKI) is one of the most common potential complications. Increasing reports have shown that M1 and M2 macrophages both take part in the progress of AKI by influencing the level of inflammatory factors and the cell death, including pyroptosis. However, whether M1 and M2 macrophages regulate AKI by secreting exosome remains unknown. In the present study, we isolated the exosomes from M1 and M2 macrophages and used Western blot and enzyme-linked immunosorbent assay (ELISA) to investigate the effect of M1 and M2 exosomes on cell pyroptosis. miRNA sequencing was used to identify the different miRNA in M1 and M2 exosomes. Luciferase reporter assay was used to verify the target gene of miRNA. We confirmed that exosomes excreted by macrophages regulated cell pyroptosis in vitro by using Western blot and ELISA. miRNA sequencing revealed the differentially expressed level of miRNAs in M1 and M2 exosomes, among which miR-93-5p was involved in the regulation of pyroptosis. By using bioinformatics predictions and luciferase reporter assay, we found that thioredoxin–interacting protein (TXNIP) was a direct target of miR-93-5p. Further in vitro and in vivo experiments indicated that exosomal miR-93-5p regulated the TXNIP directly to influence the pyroptosis in renal epithelial cells, which explained the functional difference between different phenotypes of macrophages. This study might provide new targets for the treatment of sepsis-induced AKI. |
| Keywords: | AKI exosomes macrophage miR-93 pyroptosis TXNIP |