Collagen VII Is Associated with Airway Remodeling, Honeycombing, and Fibroblast Foci in Usual Interstitial Pneumonia/Idiopathic Pulmonary Fibrosis.

Abstract

Collagen VII is an essential anchoring protein in the basement membrane zone, maintaining the attachment of stratified and pseudostratified epithelia to the underlying interstitial matrix. However, collagen VII is largely unexplored in normal lungs and idiopathic pulmonary fibrosis (IPF), a disease characterized by excessive accumulation of extracellular matrix and aberrant re-epithelialization of fibrotic lung parenchyma. Analysis of collagen VII mRNA and protein in IPF distal lungs demonstrated elevated levels compared with normal lungs. To investigate its cellular source and spatial distribution in lung tissue, immunohistochemistry, RNAscope in situ hybridization, and cell culture experiments in combination with analysis of public transcriptomic data sets were performed. In IPF lungs, collagen VII was abundant in pathologic remodeled airways and honeycomb cysts, associated with increased basal cell populations. In contrast, in the control lungs, collagen VII was mainly localized in larger airways. RNA sequencing data revealed that epithelial basal cells and keratin 5^-/keratin 17⁺ aberrant basaloid cells are the primary sources of COL7A1 expression. Furthermore, COL7A1 expression was found in mesenchymal subsets, and both collagen VII mRNA and protein were observed in fibroblast foci, another histopathologic feature of IPF. In vitro, COL7A1 expression was found to be increased in normal human lung fibroblasts treated with transforming growth factor-β1. These findings suggest that collagen VII could be involved in the process of abnormal re-epithelialization in lung fibrosis.