In:
Respiratory Research, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2021-12)
Abstract:
IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Methods Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. Results IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. Conclusion IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.
Type of Medium:
Online Resource
ISSN:
1465-993X
DOI:
10.1186/s12931-021-01858-x
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2041675-1
