59 Abnormal collagen structure resulting from lack of contribution of collagen type XIV in lungs of patients with idiopathic pulmonary fibrosis INTRODUCTION Idiopathic pulmonary fibrosis (IPF) is the result of aberrant deposition of extracellular matrix (ECM) in the alveolar septa, causing restricted breathing in patients [1]. Currently, the median survival time of patients with IPF is less than for many cancers, and there is no available cure [1]. As the lung ECM structure in IPF is drastically altered and provides a feedback loop that perpetuates disease progression [2, 3], investigating the underlying matrix pathology is expected to improve our understanding of the disease. Deposition of collagens in the altered ECM in IPF has been well documented, including an increase in collagen types I and III, as well as changes in the organization of collagen fibrils [4, 5]. Among other types of collagens, collagen type XIV (COL14) is a fibril-associated collagen with interrupted triple-helices (FACIT) that plays a crucial role in the organization of the collagen network in ECM [6]. Unlike abnormal collagen deposition and organization in IPF which has been described in detail, the role of FACITs in this process or, more specifically, involvement of COL14 in IPF, remains unknown. Previously, in a mouse model of fibrosis, higher levels of COL14 deposition were shown in bleomycin-treated mice compared to control mice [7]. However, the time for development of fibrosis in this model compared to IPF and/or species differences can influence how these results translate to humans. Accordingly, in the current study we aimed to investigate whether there are differences in the COL14 gene expression and protein levels in lung tissue from patients with (end stage) IPF compared to normal lung tissue. MATERIALS AND METHODS Data analysis of publicly available single-cell RNA-sequencing datasets Cell-type specific COL14A1 gene expression levels in lung tissue of patients with IPF and non-IPF donors were analyzed using publicly available single-cell RNA sequencing datasets from the Human Lung Cell Atlas (HCLA) consortium and the IPF atlas dataset from Adams et al. [8, 9]. These datasets were analyzed and clustered using HCLA annotations for 4 major cell groups: endothelial, epithelial, immune and stromal cells for analysis of the expression profile of the Collagen Type XIV Alpha 1 Chain (COL14A1) gene which encodes COL14 protein. 3
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