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  3. Endometrial regenerative cell exosome-derived Sirtuin 6 alleviates ulcerative colitis by remodeling macrophage polarization

Endometrial regenerative cell exosome-derived Sirtuin 6 alleviates ulcerative colitis by remodeling macrophage polarization

  • Colloids Surf B Biointerfaces. 2025 Oct 8:257:115196. doi: 10.1016/j.colsurfb.2025.115196.
Xu Liu 1,  Tong Liu 2,  Cheng-Lu Sun 3,  Bo Shao 4,  Yi-Yi Xiao 5,  Yi-Cheng Li 6,  Hong-da Wang 7,  Peng-Yu Zhao 8,  Qiang Chen 9,  Hao Wang 10
Affiliations

Affiliations

  • 1 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: lx1146076526@163.com.
  • 2 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: liutong22@tmu.edu.cn.
  • 3 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: scl17664135084@163.com.
  • 4 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: 15552849287@163.com.
  • 5 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: yeeshawlm@163.com.
  • 6 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: yichengli99@163.com.
  • 7 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: wanghd0326@163.com.
  • 8 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: zhaopengyu0109@163.com.
  • 9 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address: chenq@tmu.edu.cn.
  • 10 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China; Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, China. Electronic address: hwang1@tmu.edu.cn.
PMID: 41075762 DOI: 10.1016/j.colsurfb.2025.115196
Abstract

Macrophage dysregulation is a feature of ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD). Exosomes generated from endometrial regenerative cells (ERCs) (ERC-Exos) may influence the immunological dysfunction associated with IBD. In immunological diseases, Sirtuin 6 (SIRT6) reduces NF-κB signalling due to its protective benefits. Building on these findings, this study investigates the function and mechanism of SIRT6 derived from ERC-Exos in mediating the relief of UC. Lentiviral transduction was used to achieve SIRT6-specific knockdown ERC-Exos (SIRT6-KD-ERC-Exos). Dextran sulphate sodium (DSS)-induced ulcerative colitis in mice was categorized into untreated (PBS control), ERC-Exo-treated, and SIRT6-KD-ERC-Exo-treated groups. Compared with the untreated group, ERC-Exo treatment significantly alleviated UC-caused weight loss, bloody stools, shortening of colon length, and pathological damage. Additionally, serum cytokine levels of IL-10 and TGF-β were increased, while IL-6 and TNF-α levels were decreased. Both in the spleen and the mesenteric lymph nodes, we discovered that ERC-Exos increased M2 macrophage polarisation and decreased M1 polarisation. However, when SIRT6 was knocked down in ERC-Exos, the protective effects were compromised. Additionally, SIRT6 in ERC-Exos reduced the number of M1-polarized macrophages by blocking the NF-κB signalling pathway. This research identifies exosomal SIRT6 derived from ERCs as a potent target for modulating macrophage polarization, underscoring a promising acellular therapeutic approach for inflammatory bowel disease.

Keywords

Endometrial regenerative cells; Exosomes; Macrophage polarization; Sirtuin 6; Ulcerative colitis.

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