| Autor: |
Siwan E; Greg Brown Diabetes and Endocrine Research Laboratory, Sydney Medical School (Central), Faculty of Medicine and Health, Charles Perkin Centre, The University of Sydney, Sydney, NSW 2006, Australia., Wong J; Greg Brown Diabetes and Endocrine Research Laboratory, Sydney Medical School (Central), Faculty of Medicine and Health, Charles Perkin Centre, The University of Sydney, Sydney, NSW 2006, Australia.; Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia., Brooks BA; Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia., Shinko D; Sydney Cytometry, The University of Sydney, Sydney, NSW 2006, Australia., Baker CJ; Greg Brown Diabetes and Endocrine Research Laboratory, Sydney Medical School (Central), Faculty of Medicine and Health, Charles Perkin Centre, The University of Sydney, Sydney, NSW 2006, Australia., Deshpande N; Sydney Informatics Hub, The University of Sydney, Sydney, NSW 2006, Australia., McLennan SV; Greg Brown Diabetes and Endocrine Research Laboratory, Sydney Medical School (Central), Faculty of Medicine and Health, Charles Perkin Centre, The University of Sydney, Sydney, NSW 2006, Australia.; NSW Health Pathology, Sydney, NSW 2050, Australia., Twigg SM; Greg Brown Diabetes and Endocrine Research Laboratory, Sydney Medical School (Central), Faculty of Medicine and Health, Charles Perkin Centre, The University of Sydney, Sydney, NSW 2006, Australia.; Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia., Min D; Greg Brown Diabetes and Endocrine Research Laboratory, Sydney Medical School (Central), Faculty of Medicine and Health, Charles Perkin Centre, The University of Sydney, Sydney, NSW 2006, Australia.; Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia. |
| Abstrakt: |
CD163, a scavenger receptor with anti-inflammatory function expressed exclusively on monocytes/macrophages, is dysregulated in cases of diabetes complications. This study aimed to characterize circulating CD163+ monocytes in the presence (D +Comps ) or absence (D -Comps ) of diabetes-related complications. RNA-sequencing and mass cytometry were conducted on CD163+ monocytes in adults with long-duration diabetes and D +Comps or D -Comps . Out of 10,868 differentially expressed genes identified between D +Comps and D -Comps , 885 were up-regulated and 190 were down-regulated with a ≥ 1.5-fold change. In D +Comps , 'regulation of centrosome cycle' genes were enriched 6.7-fold compared to the reference genome. MIR27A, MIR3648-1, and MIR23A , the most up-regulated and CD200R1 , the most down-regulated gene, were detected in D +Comps from the list of 75 'genes of interest'. CD163+ monocytes in D +Comps had a low proportion of recruitment markers CCR5, CD11b, CD11c, CD31, and immune regulation markers CD39 and CD86. A gene-protein network identified down-regulated TLR4 and CD11b as 'hub-nodes'. In conclusion, this study reports novel insights into CD163+ monocyte dysregulation in diabetes-related complications. Enriched centrosome cycle genes and up-regulated miRNAs linked to apoptosis, coupled with down-regulated monocyte activation, recruitment, and immune regulation, suggest functionally distinct CD163+ monocytes in cases of diabetes complications. Further investigation is needed to confirm their role in diabetes-related tissue damage. |
