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Series GSE183657 Query DataSets for GSE183657
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
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.
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.
Contributor(s) Fan X, Geng Y, Li L, Noth I, Huang Y, Liu J
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BioProject PRJNA749378
Submission date Sep 08, 2021
Last update date Oct 20, 2021
Contact name Yong Huang
Phone (434) 243-0842
Organization name University of Viginia
Department Medicine
Street address 1340 Jefferson Park Ave
City Charlottesville
State/province VA
ZIP/Postal code 22908
Country USA
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (12)
GSM5567103 Wild-type Vehicle, rep1
GSM5567104 Wild-type Vehicle, rep2
GSM5567105 Wild-type Vehicle, rep3

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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
Raw data are available in SRA
Processed data are available on Series record

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