PEAR1 regulates expansion of activated fibroblasts and deposition of extracellular matrix in pulmonary fibrosis

Yan Geng, Lin Li, Jie Yan, Kevin Liu, Aizhen Yang, Lin Zhang, Yingzhi Shen, Han Gao, Xuefeng Wu, Imre Noth, Yong Huang, Junling Liu () and Xuemei Fan ()
Additional contact information
Yan Geng: Shanghai Jiao Tong University School of Medicine
Lin Li: Shanghai Jiao Tong University School of Medicine
Jie Yan: Shanghai Jiao Tong University School of Medicine
Kevin Liu: Vanderbilt University
Aizhen Yang: Soochow University
Lin Zhang: Shanghai Jiao Tong University School of Medicine
Yingzhi Shen: Shanghai Jiao Tong University School of Medicine
Han Gao: Beijing Normal University
Xuefeng Wu: Shanghai Jiao Tong University School of Medicine
Imre Noth: University of Virginia
Yong Huang: University of Virginia
Junling Liu: Shanghai Jiao Tong University School of Medicine
Xuemei Fan: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Pulmonary fibrosis is a chronic interstitial lung disease that causes irreversible and progressive lung scarring and respiratory failure. Activation of fibroblasts plays a central role in the progression of pulmonary fibrosis. Here we show that platelet endothelial aggregation receptor 1 (PEAR1) in fibroblasts may serve as a target for pulmonary fibrosis therapy. Pear1 deficiency in aged mice spontaneously causes alveolar collagens accumulation. Mesenchyme-specific Pear1 deficiency aggravates bleomycin-induced pulmonary fibrosis, confirming that PEAR1 potentially modulates pulmonary fibrosis progression via regulation of mesenchymal cell function. Moreover, single cell and bulk tissue RNA-seq analysis of pulmonary fibroblast reveals the expansion of Activated-fibroblast cluster and enrichment of marker genes in extracellular matrix development in Pear1−/− fibrotic lungs. We further show that PEAR1 associates with Protein Phosphatase 1 to suppress fibrotic factors-induced intracellular signalling and fibroblast activation. Intratracheal aerosolization of monoclonal antibodies activating PEAR1 greatly ameliorates pulmonary fibrosis in both WT and Pear1-humanized mice, significantly improving their survival rate.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34870-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34870-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34870-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().