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

Abstract Type VI collagen (COL6) is a key extracellular matrix protein that supports matrix organization and cell-matrix interactions, yet its regulation in idiopathic pulmonary fibrosis (IPF) remains poorly understood. Here, we characterize COL6 gene expression, spatial localization, remodeling, and functional effects of COL6-derived fragments. Analysis of publicly available single-cell RNA sequencing data from 30 controls and 32 pulmonary fibrosis patients revealed higher expression of COL6A1–A6 in fibrotic lungs, predominantly in mesenchymal cells ( A1 : p=0.0002, A2 : p=0.0005, A3 : p=2.5x10 -5 , A5 : p=0.016, A6 : p=0.007). Immunohistochemical analysis of lung tissue from never-smoker (n=9), ex-smoker (n=9) controls, and IPF patients (n=12) showed extensive COL6 localization across parenchyma, airways, and vessels. The proportion of COL6α1 and COL6α2 was lower around IPF vessels (α1: p