Qualitative rather than quantitative changes are hallmarks of fibroblasts in bleomycin-induced pulmonary fibrosis

Pulmonary fibrosis is characterized by accumulation of activated fibroblasts that produce excessive amounts of extracellular matrix components such as collagen type I. However, the dynamics and activation signatures of fibroblasts during fibrogenesis remain poorly understood, especially in vivo. We...

Full description

Saved in:
Bibliographic Details
Published in:The American journal of pathology Vol. 183; no. 3; p. 758
Main Authors: Tsukui, Tatsuya, Ueha, Satoshi, Abe, Jun, Hashimoto, Shin-ichi, Shichino, Shigeyuki, Shimaoka, Takeshi, Shand, Francis H W, Arakawa, Yasuka, Oshima, Kenshiro, Hattori, Masahira, Inagaki, Yutaka, Tomura, Michio, Matsushima, Kouji
Format: Journal Article
Language:English
Published: United States 01.09.2013
Subjects:
Animals
Apoptosis
Biomarkers - metabolism
Bleomycin
Bone Marrow Cells - pathology
Cell Proliferation
Collagen Type I - metabolism
Fibroblasts - metabolism
Fibroblasts - pathology
Gene Expression Profiling
Gene Ontology
Green Fluorescent Proteins - metabolism
Lung - metabolism
Lung - pathology
Mice
Mice, Inbred C57BL
Osteopontin - metabolism
Pulmonary Fibrosis - metabolism
Pulmonary Fibrosis - pathology
Recombinant Fusion Proteins - metabolism
Up-Regulation - genetics
ISSN:1525-2191, 1525-2191
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pulmonary fibrosis is characterized by accumulation of activated fibroblasts that produce excessive amounts of extracellular matrix components such as collagen type I. However, the dynamics and activation signatures of fibroblasts during fibrogenesis remain poorly understood, especially in vivo. We examined changes in lung tissue cell populations and in the phenotype of activated fibroblasts after acute injury in a model of bleomycin-induced pulmonary fibrosis. Despite clustering of collagen type I-producing fibroblasts in fibrotic regions, flow cytometry-based quantitative analysis of whole lungs revealed that the number of fibroblasts in the lungs remained constant. At the peak of inflammation, fibroblast proliferation and apoptosis were both increased, suggesting that the clustering was not merely a result of proliferation, but also of fibroblast migration from nearby alveolar walls. Parabiosis experiments demonstrated that fibroblasts were not supplied from the circulation. Comprehensive gene expression analysis of freshly isolated fibroblasts revealed a detailed activation signature associated with fibrogenesis, including changes in genes responsible for migration and extracellular matrix construction. The Spp1 gene, which encodes osteopontin, was highly up-regulated and was an identifying characteristic of activated fibroblasts present at the sites of remodeling. Osteopontin may serve as a useful marker of profibrotic fibroblasts. These results provide insights into the cellular and molecular mechanisms underlying pulmonary fibrosis and provide a foundation for development of specific antifibrotic therapies.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1525-2191
1525-2191
DOI:10.1016/j.ajpath.2013.06.005