TABLE 1

MUC1 expression and participation in respiratory diseases

DiseaseMUC1 expressionRole of MUC1
Infectious diseases
Pseudomonas aeruginosaUpregulated in lung epithelial cells [35, 36] and alveolar macrophages [39]During late-stage infection:
  •  Downregulation of TLR5 (epithelial cells)-induced [35, 36] and TLR4 (macrophages)-induced [39] inflammation

  •  Promotion of neutrophil apoptosis [35, 36]

Haemophilus influenzaeUpregulated in airway epithelial cells [27]During late-stage infection:
  •  Downregulation of TLR2-induced inflammation [27]

 Respiratory syncytial virusUpregulated in airway epithelial cells [28, 42]During last stage infection:
  •  Downregulation of TLR3-induced inflammation [28, 42]

CRSwNP
 Corticosteroid respondersUpregulated in NP epithelium [54]MUC1-CT/GRα nuclear translocation: anti-inflammatory effects [5]
 Corticosteroid resistantDownregulated in NP epithelium [5]
  • Overactivation of TLR2/5-induced inflammation [5]

  • GR-Ser226 hyperphosphorylation [5]

  • Reduced formation of the MUC1-CT/GRα nuclear transcription complex [5]

Asthma
 Mild asthma (corticosteroid responders)Normal expression levels in HBECs and neutrophilsMUC1-CT/GRα nuclear translocation: anti-inflammatory effects [5]
 Severe asthma (corticosteroid resistant)Downregulation in HBECs and neutrophils [6]
  • GR-Ser226 hyperphosphorylation [6]

  • Reduced formation of the MUC1-CT/GRα nuclear transcription complex [6]

  • Impairment of glucocorticoid antinecroptotic effects [67]

  • Enhancing of viral and bacterial-induced TLR signalling [30]

 Paediatric acute exacerbation [62]Elevated KL-6 serum levelsBiomarker
COPD
 Corticosteroid respondersNormal expression levels in lung tissue, bronchial epithelial cells and sputum neutrophilsMUC1-CT/GRα nuclear translocation: anti-inflammatory effects [5]
 Corticosteroid resistant without recent exacerbationDownregulated in lung tissue, bronchial epithelial cells, and sputum neutrophils [7]
  • GR-Ser226 hyperphosphorylation [6]

  • Reduced formation of the MUC1-CT/GRα nuclear transcription complex

 Acute exacerbation
  • Upregulated MUC1-CT in sputum [75]

  • Elevated MUC1-EC levels in sputum [72, 76]

  • Protective role

  • Biomarker

Lung cancer
 Paclitaxel no responders
  • Overexpression and depolarisation in epithelial cells [77]

  • Increased CA15-3 serum levels [84, 85]

  • Inhibition of lung cancer cell apoptosis [92]

  • Induction of cell proliferation [93]

  • Induction of EMT [93]

  • Induction of PD-L1 expression: evasion from immune recognition [110]

  • Biomarker

 EGFR-TKI no respondersEnhanced MUC1-C expression [104]Biomarker for predicting the efficacy of lung cancer treatments
 EGFR-TKI partial responders
  • High serum KL-6 levels prior to treatment [106, 107]

  • Increased serum KL-6 levels after EGFR-TKI treatment [106]

Reduced serum KL-6 levels after EGFR-TKI treatment
ILDs
 Hypersensitivity pneumonitisElevated KL-6 serum levels [123, 127–132]Biomarker [122, 124, 128–132]
 Sarcoidosis
 Radiation pneumonitis
 Drug-induced interstitial pneumonitis
 Collagen vascular disease-associated IP
 Nonspecific IP
 IPF
  • Elevated KL-6 serum/BALF levels [131–133]

  • Elevated serum KL-6 levels during IPF acute exacerbations [134]

  • MUC1-CT overexpression in hyperplastic ATII cells and fibroblasts [117, 140]

  • Biomarker [131–134, 138]

  • MUC1-CT collaboration with TGF-β1 and galectin-3 to form a MUC1-CT/phospho-Smad3/active-β-catenin nuclear protein complex to promote [140]:

    • EMT

    • FMT

    • Fibroblast proliferation

    • ATII and fibroblast senescence

  • MUC1/ICAM-1 association to induce cytoskeletal changes and motility [144]

MUC1: mucin 1; TLR: toll-like receptor; CRSwNP: chronic rhinosinusitis with nasal polyps; NP: nasal polyps; MUC1-CT: MUC1 cytoplasmic tail; GR: glucocorticoid receptor; HBEC: human bronchial epithelial cell; ILD: interstitial lung disease; IP: interstitial pneumonia; KL-6: Krebs von den Lungen-6; MUC1-EC: MUC1 extracellular; EMT: epithelial to mesenchymal transition; PD-L1: programmed death ligand 1; EGFR-TKI: epidermal growth factor receptor–tyrosine kinase inhibitor; IPF: idiopathic pulmonary fibrosis; BALF: bronchoalveolar lavage fluid; TGF-β1: transforming growth factor-β1; FMT: fibroblast to mesenchymal transition; ATII: alveolar type II cells; ICAM-1: intracellular adhesion molecule-1.