Summary of ssbd-repos-000288

SSBD:repository
SSBD:repository URL
DOI
Title
Autocrine TGF-β-positive feedback in profibrotic AT2-lineage cells plays a crucial role in non-inflammatory lung fibrogenesis
Description

The molecular etiology of idiopathic pulmonary fibrosis (IPF) has been extensively investigated to identify new therapeutic targets. While anti-inflammatory treatment is not effective for IPF patients, researchers have found that damaged alveolar epithelial cells play a critical role in lung fibrogenesis. Here, we established organoid-based lung fibrosis model using mouse and human lung tissue to assess direct communication between damaged alveolar type II (AT2)-lineage cells and lung fibroblasts by excluding immune cells. Using this in vitro model and mouse genetics, we demonstrated that bleomycin causes DNA damage and activates p53 signaling in AT2-lineage cells, leading to AT2-to-AT1 transition-like state with a senescence-associated secretory phenotype (SASP). Among SASP-related factors, TGF-β played an exclusive role in promoting lung fibroblast-to-myofibroblast differentiation. Moreover, the autocrine TGF-β-positive feedback loop in AT2-lineage cells is a critical cellular system in non-inflammatory lung fibrogenesis. These findings provide insights into the mechanism of IPF and identified potential therapeutic targets.

Submited Date
2023-04-10
Release Date
2023-07-11
Updated Date
-
License
Data size
1.3 GB
Data formats
PNG, JPEG

Organism
Mus musculus, Homo sapiens
Strain
-
Cell Line
-
Molecular Function (MF)
-
Biological Process (BP)
-
Cellular Component (CC)
-
Study Type
-
Imaging Methods
-

Method Summary
-

Contact(s)
Mitsuru Morimoto
Organization(s)
RIKEN Center for Biosystems Dynamics Research , Laboratory for Lung Development and Regeneration
Image Data Contributors
Yasunori Enomoto, Yasunori Enomoto
Quantitative Data Contributors
Yasunori Enomoto

Download files
Download zipped files