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Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review)

  • Authors:
    • Peter Muro
    • Caihong Jing
    • Yaru Qiao
    • Wenbing Wang
    • Bo Wang
    • Fei Mao
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, Jiangsu 212300, P.R. China
    Copyright: © Muro et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 135
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    Published online on: July 3, 2025
       https://doi.org/10.3892/ijmm.2025.5576
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Abstract

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis and Crohn's disease, poses significant treatment difficulties because of its persistent course and underlying inflammatory mechanisms. Existing treatments primarily focus on alleviating symptoms, while novel biological drugs that target specific molecular pathways could address the root causes of the disease. One such pathway involves the farnesoid X receptor (FXR), a nuclear receptor essential for bile acid metabolism, intestinal homeostasis and modulation of inflammation. Activating FXR can reduce intestinal inflammation and improve gut barrier function, highlighting its potential as a treatment target for IBD. However, using synthetic agonists to directly activate FXR has drawbacks, including off‑target effects and limited effectiveness. Exosomes, tiny nanoscale vesicles involved in cell‑to‑cell communication, have emerged as promising therapeutic tools for regulating FXR signaling in IBD. Exosomes, particularly those derived from mesenchymal stem cells, can deliver bioactive molecules that promote FXR activation, reduce inflammation, and enhance tissue regeneration. The present review examines how exosomes regulate FXR signaling and their potential therapeutic use in IBD. It covers exosome biogenesis, therapeutic benefits and their molecular mechanisms in IBD.
View Figures

Figure 1

Exosome biogenesis follows a
sequential pathway, starting with the formation of early endosomes
through endocytosis. These early endosomes then mature into late
endosomes, which subsequently transform into MVBs through the
inward budding of the endosomal membrane, trapping cargo within
ILVs. Ultimately, the MVBs either merge with lysosomes for cargo
degradation or fuse with the plasma membrane, releasing ILVs as
exosomes into the extracellular environment. MVBs, multivesicular
bodies; ILVs, intraluminal vesicles.

Figure 2

Classification of macrophages into M1
and M2 subtypes. M1 macrophages can be activated by LPS and INF-γ,
and display and secrete various proinflammatory cytokines and
chemokines, including TNF-α, IL-6, IL-1α, CXCL9 and CXCL10. M2
macrophages are stimulated by IL-4 and IL-13, secreting various
anti-inflammatory mediators, including IL-10, TGF-β, CCL1 and
CCL17, which help suppress the immune inflammatory response and
promote tissue repair in IBD. LPS, lipopolysaccharide; IBD,
inflammatory bowel disease.

Figure 3

FXR consists of two key domains: 1)
the ligand-binding domain, which interacts with bile acids, and 2)
the DNA-binding domain, responsible for gene regulation (denoted by
black arrows). FXR exhibits high expression levels in the kidney,
intestines and liver, with green arrows highlighting its tissue
specificity. The NR1H4 gene is associated with FXR (indicated by a
black arrow), underscoring their functional relationship. FXR plays
a regulatory role in BA synthesis and enterohepatic circulation,
with molecular symbols representing BA and its connection to genes
such as CYP7A1 and BSEP. Additionally, FXR modulates critical
metabolic pathways, including lipid metabolism and glucose
homeostasis, as depicted by black arrows. FXR, Farnesoid X
receptor; BA, bile acid; BSEP, bile salt export pump.

Figure 4

FXR serves as a key regulator, with
three radiating pathways: (1)
Modulation of the immune response, (2) Maintenance of gut microbiota, and
(3) Maintenance of intestinal
barrier integrity. IBD links these pathways, emphasizing how
dysregulation of FXR contributes to the development of IBD by
disrupting immune function, promoting inflammation, and impairing
barrier integrity, as depicted by black arrow. FXR, Farnesoid X
receptor; IBD, inflammatory bowel disease.
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Copy and paste a formatted citation
Spandidos Publications style
Muro P, Jing C, Qiao Y, Wang W, Wang B and Mao F: Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review). Int J Mol Med 56: 135, 2025.
APA
Muro, P., Jing, C., Qiao, Y., Wang, W., Wang, B., & Mao, F. (2025). Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review). International Journal of Molecular Medicine, 56, 135. https://doi.org/10.3892/ijmm.2025.5576
MLA
Muro, P., Jing, C., Qiao, Y., Wang, W., Wang, B., Mao, F."Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review)". International Journal of Molecular Medicine 56.3 (2025): 135.
Chicago
Muro, P., Jing, C., Qiao, Y., Wang, W., Wang, B., Mao, F."Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review)". International Journal of Molecular Medicine 56, no. 3 (2025): 135. https://doi.org/10.3892/ijmm.2025.5576
Copy and paste a formatted citation
x
Spandidos Publications style
Muro P, Jing C, Qiao Y, Wang W, Wang B and Mao F: Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review). Int J Mol Med 56: 135, 2025.
APA
Muro, P., Jing, C., Qiao, Y., Wang, W., Wang, B., & Mao, F. (2025). Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review). International Journal of Molecular Medicine, 56, 135. https://doi.org/10.3892/ijmm.2025.5576
MLA
Muro, P., Jing, C., Qiao, Y., Wang, W., Wang, B., Mao, F."Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review)". International Journal of Molecular Medicine 56.3 (2025): 135.
Chicago
Muro, P., Jing, C., Qiao, Y., Wang, W., Wang, B., Mao, F."Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review)". International Journal of Molecular Medicine 56, no. 3 (2025): 135. https://doi.org/10.3892/ijmm.2025.5576
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