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September 17, 2026AJP Cell Physiology

Type VI collagen is proportionally lower around airways and blood vessels in idiopathic pulmonary fibrosis

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Authors

HBHelene W. BreisnesMNMehmet NizamogluMNMaunick Lefin Koloko Ngassie

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Overview

Tissue and transcriptomic analysis reveals reduced vascular and airway type VI collagen in idiopathic pulmonary fibrosis, suggesting altered matrix remodeling promotes fibroblast survival.

Key Points

  • To characterize type VI collagen (COL6) gene expression, spatial localization, remodeling fragments, and functional effects in idiopathic pulmonary fibrosis (IPF).
  • Analyzed COL6 gene expression in publicly available single-cell RNA sequencing data from 30 controls and 32 pulmonary fibrosis patients.
  • Conducted immunohistochemical analysis of COL6 localization and quantified remodeling markers (PRO-C6, C6M) in lung tissue from never-smoker controls (n=3–9), ex-smoker controls (n=5–9), and IPF patients (n=10–12).
  • Evaluated the functional effects of COL6 and PRO-C6 on cell viability and apoptosis across fibroblasts, epithelial cells, and endothelial cells.
  • Mesenchymal cells in fibrotic lungs exhibited significantly higher COL6A1–A6 gene expression compared to controls (COL6A1: p=0.0002; COL6A2: p=0.0005; COL6A3: p=2.5x10⁻⁵; COL6A5: p=0.016; COL6A6: p=0.007).
  • The proportion of COL6α1 and COL6α2 was significantly lower around IPF vessels (α1: p<0.001; α2: p=0.012) and COL6α2 was lower around IPF airways (p=0.033) compared with never-smoker controls; PRO-C6 synthesis was lower in IPF airways (p=0.0075) and C6M degradation was lower throughout IPF tissue (p=0.0008).
  • COL6 and PRO-C6 increased fibroblast viability (COL6: p=0.002; PRO-C6: p=0.0021) without altering apoptosis, with comparable viability trends observed in epithelial and endothelial cells.

Cite This Study

Breisnes et al. (2026) studied this question.

synapsesocial.com/papers/6aabb69c5f706d05830e51a1https://doi.org/10.1152/ajpcell.00034.2026
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1A74-02 Disrupted Type VI Collagen Localization Around Airways and Blood Vessels in the IPF Lung2026
  2. 2C71-22 Collagen Prolyl-3-hydroxylase 1 Is Widely Expressed in Lung Structural Cells and Counteracts TGF-β2 Mediated Profibrotic Signaling2026
  3. 3Circulating biomarkers reflecting type III, IV and VI collagen remodeling are present in lung tissue of patients with pulmonary fibrosis and non-fibrotic controls2026
  4. 4Epithelial PCSK6 Promotes Proliferation and Decreases Collagen Deposition by Fibroblasts Potentially via MMP Activation2026
  5. 5FK506-binding protein 10 (FKBP10) regulates lung fibroblast migration via collagen VI synthesis2018 · 38 citations