ArticleInternational journal of nanomedicine2025
MiRNA Let-7i-5p-Contained Small Extracellular Vesicles from Macrophages Induce Nucleus Pulposus Cell Senescence via Targeting LIN28A.
Article in International journal of nanomedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Harnessing Natural Extracellular Vesicles to Combat Age-Related Diseases: From Aging Drivers to Therapeutic Opportunities.International journal of nanomedicine · 2026Review
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Purpose: To investigate the role of macrophage-derived small extracellular vesicles (MΦ-sEVs) in nucleus pulposus (NP) cell (NPC) senescence and screen the pro-senescent micro-RNA (miRNA) in MΦ-sEVs and potential mRNA targets. Methods: Bone marrow-derived macrophage (BMDM)-derived sEVs were isolated by differential centrifugation, and the phenotypes of MΦ-sEVs were identified. NPCs were treated with MΦ-sEVs, and cellular senescence levels were examined by senescence-associated β-galactosidase (SA‑β‑Gal) staining and Western blotting (WB). Activation of the senescence-associated secretory phenotype (SASP) was tested using qRT-PCR and cytometric bead arrays (CBA). LPS+IFNγ-MΦ-sEVs or IL-4-MΦ-sEVs were injected into the rat coccygeal NP tissues to determine the in vivo effects of MΦ-sEVs on intervertebral disc degeneration (IVDD) and NPC senescence. The miRNA levels in MΦ-sEVs were evaluated using PANDORA sequencing. NPCs were transfected with miRNA mimics or inhibitors to screen the miRNAs with pro-senescence effects. Results: MΦ-sEVs displayed the cup-shaped morphology, with diameters mainly ranging from 40 to 200 nm. Both LPS+IFNγ-MΦ-sEVs and IL-4-MΦ-sEVs impaired NPC viability and accelerated NPC senescence. The expression levels of SASP and senescence-related proteins, including p16, p21, and p53, were elevated by MΦ-sEVs treatment. Animal experiments indicated that LPS+IFNγ-MΦ-sEVs or IL-4-MΦ-sEVs exacerbated IVDD with increased p16-positive cell ratio and activated SASP. PANDORA sequencing of MΦ-sEVs revealed high levels of let-7i-5p, which exerted pro-senescence effects by downregulating LIN28A expression. Inhibiting or silencing LIN28A by C1632 or specific siRNAs also triggered NPC senescence. Conclusion: Both LPS+IFNγ-MΦ-sEVs and IL-4-MΦ-sEVs induced NPC senescence by delivering miRNA let-7i-5p to inhibit LIN28A.
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