Immunity, inflammation and disease · 2026
TGF-β/Smad-Associated Epithelial-Fibroblast Remodeling Underlies Collagen Deposition in Chronic Rhinosinusitis With Nasal Polyps.
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Liu Shilong, Xie Peizheng, Deng Hanwei, Zhu Zhenhua
Аннотация
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently accompanied by epithelial barrier disruption and tissue remodeling. This study aimed to investigate whether epithelial-mesenchymal transition (EMT), fibroblast activation, collagen deposition, and TGF-β/Smad signaling are coordinated during CRSwNP nasal mucosal remodeling.
MATERIALS AND METHODS: Publicly available single-cell RNA sequencing datasets from two independent human cohorts were integrated to characterize epithelial, fibroblast, and myeloid heterogeneity, disease-associated transcriptional changes, pseudotime dynamics, and cell-cell communication, with CellChat applied to the COLLAGEN and TGF-β signaling modules. Immunofluorescence, Masson's trichrome, and periodic acid-Schiff (PAS) staining were performed on nasal polyps from CRSwNP patients and control nasal mucosa. An ovalbumin (OVA)/Staphylococcus aureus enterotoxin B (SEB)-induced CRSwNP-like mouse model, including a dexamethasone intervention arm, was used for histopathological, immunofluorescence, and Western blot validation.
RESULTS: In CRSwNP, fibroblasts shifted toward activated, matrix-remodeling states, and epithelial cells displayed enhanced injury-repair and EMT-related features, while TGFB1 was preferentially detected in a GPNMB-expressing macrophage subset expanded in polyps. Potential epithelial-fibroblast communication was enriched within COLLAGEN and TGF-β modules, with TGFB1-TGFBR1/TGFBR2 and COL1A1-SDC4/CD44 emerging as candidate ligand-receptor pairs. Human polyps showed collagen deposition, α-SMA-high fibroblast enrichment, EMT-like epithelial changes, and nuclear p-Smad3 accumulation. The mouse model recapitulated this pattern, and dexamethasone partially reversed it at the protein level.
DISCUSSION: Integrating human single-cell transcriptomics with tissue- and protein-level validation, this study characterizes a coordinated, TGF-β/Smad3-associated epithelial-fibroblast remodeling program underlying collagen deposition in CRSwNP. These candidate axes, together with a macrophage source of TGFB1, offer mechanistic clues to epithelial-fibroblast-immune crosstalk; their partial reversibility by dexamethasone supports pathway-targeted anti-remodeling strategies, while causal roles await spatial and functional validation.
MATERIALS AND METHODS: Publicly available single-cell RNA sequencing datasets from two independent human cohorts were integrated to characterize epithelial, fibroblast, and myeloid heterogeneity, disease-associated transcriptional changes, pseudotime dynamics, and cell-cell communication, with CellChat applied to the COLLAGEN and TGF-β signaling modules. Immunofluorescence, Masson's trichrome, and periodic acid-Schiff (PAS) staining were performed on nasal polyps from CRSwNP patients and control nasal mucosa. An ovalbumin (OVA)/Staphylococcus aureus enterotoxin B (SEB)-induced CRSwNP-like mouse model, including a dexamethasone intervention arm, was used for histopathological, immunofluorescence, and Western blot validation.
RESULTS: In CRSwNP, fibroblasts shifted toward activated, matrix-remodeling states, and epithelial cells displayed enhanced injury-repair and EMT-related features, while TGFB1 was preferentially detected in a GPNMB-expressing macrophage subset expanded in polyps. Potential epithelial-fibroblast communication was enriched within COLLAGEN and TGF-β modules, with TGFB1-TGFBR1/TGFBR2 and COL1A1-SDC4/CD44 emerging as candidate ligand-receptor pairs. Human polyps showed collagen deposition, α-SMA-high fibroblast enrichment, EMT-like epithelial changes, and nuclear p-Smad3 accumulation. The mouse model recapitulated this pattern, and dexamethasone partially reversed it at the protein level.
DISCUSSION: Integrating human single-cell transcriptomics with tissue- and protein-level validation, this study characterizes a coordinated, TGF-β/Smad3-associated epithelial-fibroblast remodeling program underlying collagen deposition in CRSwNP. These candidate axes, together with a macrophage source of TGFB1, offer mechanistic clues to epithelial-fibroblast-immune crosstalk; their partial reversibility by dexamethasone supports pathway-targeted anti-remodeling strategies, while causal roles await spatial and functional validation.