NDLI: Early events marking lung fibroblast transition to profibrotic state in idiopathic pulmonary fibrosis

Content Provider	Springer Nature : BioMed Central
Author	Jia, Minxue Rosas, Lorena Kapetanaki, Maria G. Tabib, Tracy Sebrat, John Cruz, Tamara Bondonese, Anna Mora, Ana L. Lafyatis, Robert Rojas, Mauricio Benos, Panayiotis V.
Abstract	Background Idiopathic Pulmonary Fibrosis (IPF) is an age-associated progressive lung disease with accumulation of scar tissue impairing gas exchange. Previous high-throughput studies elucidated the role of cellular heterogeneity and molecular pathways in advanced disease. However, critical pathogenic pathways occurring in the transition of fibroblasts from normal to profibrotic have been largely overlooked. Methods We used single cell transcriptomics (scRNA-seq) from lungs of healthy controls and IPF patients (lower and upper lobes). We identified fibroblast subclusters, genes and pathways associated with early disease. Immunofluorescence assays validated the role of MOXD1 early in fibrosis. Results We identified four distinct fibroblast subgroups, including one marking the normal-to-profibrotic state transition. Our results show for the first time that global downregulation of ribosomal proteins and significant upregulation of the majority of copper-binding proteins, including MOXD1, mark the IPF transition. We find no significant differences in gene expression in IPF upper and lower lobe samples, which were selected to have low and high degree of fibrosis, respectively. Conclusions Early events during IPF onset in fibroblasts include dysregulation of ribosomal and copper-binding proteins. Fibroblasts in early stage IPF may have already acquired a profibrotic phenotype while hallmarks of advanced disease, including fibroblast foci and honeycomb formation, are still not evident. The new transitional fibroblasts we discover could prove very important for studying the role of fibroblast plasticity in disease progression and help develop early diagnosis tools and therapeutic interventions targeting earlier disease states.
Related Links	https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-023-02419-0.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12931-023-02419-0
Journal	Respiratory Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2023-04-21
Access Restriction	Open
Subject Keyword	Pneumology Respiratory System Idiopathic Pulmonary Fibrosis Fibroblasts Copper Ribosomal proteins MOXD1 scRNA-seq Pneumology/Respiratory System
Content Type	Text
Resource Type	Article
Subject	Pulmonary and Respiratory Medicine
Journal Impact Factor	4.7/2023
5-Year Journal Impact Factor	5.3/2023

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