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| Status |
Public on Oct 20, 2021 |
| Title |
Monoclonal Antibody Targeting Pear1 for Pulmonary Fibrosis Therapy [bulk RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pulmonary fibrosis (PF) is a chronic interstitial lung disease that causes irreversible and progressive lung scarring and respiratory failure. Activation of fibroblasts (FBs) play a central role in progression of PF. Here we report that platelet endothelial aggregation receptor 1 (Pear1) in FBs is a new molecular target for PF therapy. Pear1 deficiency spontaneously caused respiratory function decline and alveolar collagens accumulation in old mice. The degree of PF and mortality induced by bleomycin were significantly enhanced in Pear1 deficient mice. FB Mesenchyme-specific Pear1 deficiency aggravated bleomycin-induced PF, confirming that Pear1 modulates PF progression probably byvia regulation of FBs function. Single cell RNA-seq analysis of pulmonary FB and functional enrichment analysis revealed drastic expansion of Aactivated- FB clusters and enrichment of activated FB marker genes in extracellular matrix (ECM) development and pulmonary fibrosis in Pear1-/- fibrotic lungs. CD140+ bulk tissue RNA-seq analysis further confirmed that multiple mesenchyme development pathways especially epithelial mesenchymal transition (EMT) are enriched with up-regulated genes involving FB mediated ECM organization and development in in Pear1-/- fibrotic lungs. We further found that Pear1 associated with Protein Phosphatase 1 to suppress fibrotic factors such as TGFß, FGF or PDGF-induced intracellular signalling and FB activation. Intratracheal aerosolization of monoclonal antibody activating Pear1 greatly ameliorates PF in both wild-type mice and Pear1-humanized mice, suggesting that targeting Pear1 may serve as a new therapeutic strategy for PFand significantly improves their survival rate.
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| Overall design |
Fresh lung tissues were harvested from mouse bleomycin model. We used flow cytometry to sort out Cd140+ cells from total lung cells. Total RNA were isolated from the cells and used for RNA-seq assay.
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| Contributor(s) |
Fan X, Geng Y, Li L, Noth I, Huang Y, Liu J |
| Citation(s) |
36402779 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 HL130796 |
Architectural structure and regulation of TOLLIP in IPF |
UNIVERSITY OF VIRGINIA CHARLOTTESVILLE |
Imre Noth |
| UG3 HL145266 |
1/2 Prospective tReatment EffiCacy in IPF uSlng genOtype for Nac Selection (PRECISIONS) trial and Molecular Endophenotyping in Idiopathic Pulmonary Fibrosis and Interstitial Lung Diseases study |
WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY |
Imre Noth |
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| BioProject |
PRJNA749378 |
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| Submission date |
Sep 08, 2021 |
| Last update date |
Nov 21, 2022 |
| Contact name |
Yong Huang |
| E-mail(s) |
[email protected]
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| Phone |
(434) 243-0842
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| Organization name |
University of Viginia
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| Department |
Medicine
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| Street address |
1340 Jefferson Park Ave
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22908 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE183657_normalized.expression.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE183657_raw.counts.txt.gz |
803.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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