TGF‐β/Smad‐Associated Epithelial–Fibroblast Remodeling Underlies Collagen Deposition in Chronic Rhinosinusitis With Nasal Polyps
- 1The First Clinical College of Traditional Chinese Medicine Hunan University of Traditional Chinese Medicine Changsha China
- 2Department of Otorhinolaryngology–Head and Neck Surgery First Affiliated Hospital of Hunan University of Traditional Chinese Medicine Changsha Hunan China
Abstract
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.
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BibTeX
@article{liu2026tgfβsmadassociated,
title = {{TGF‐β/Smad‐Associated Epithelial–Fibroblast Remodeling Underlies Collagen Deposition in Chronic Rhinosinusitis With Nasal Polyps}},
author = {Shilong Liu and Peizheng Xie and Hanwei Deng and Zhenhua Zhu},
journal = {Immunity, Inflammation and Disease},
year = {2026},
month = oct,
doi = {10.1002/iid3.70532},
url = {https://doi.org/10.1002/iid3.70532},
note = {CC BY},
}
RIS
TY - JOUR
TI - TGF‐β/Smad‐Associated Epithelial–Fibroblast Remodeling Underlies Collagen Deposition in Chronic Rhinosinusitis With Nasal Polyps
AU - Shilong Liu
AU - Peizheng Xie
AU - Hanwei Deng
AU - Zhenhua Zhu
PY - 2026
DA - 2026/10/30
JO - Immunity, Inflammation and Disease
DO - 10.1002/iid3.70532
UR - https://doi.org/10.1002/iid3.70532
AB - 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.
SN - 2050-4527
ER -