Article ; Online: C-MYC induces idiopathic pulmonary fibrosis via modulation of miR-9-5p-mediated TBPL1.
2022 Volume 93, Page(s) 110274
Abstract: We sought to pinpoint the potential role of C-MYC in pulmonary fibroblast proliferation in idiopathic pulmonary fibrosis (IPF) and its mechanism. A mouse model of IPF was established by injection of bleomycin. C-MYC and miR-9-5p expression was determined ...
Abstract | We sought to pinpoint the potential role of C-MYC in pulmonary fibroblast proliferation in idiopathic pulmonary fibrosis (IPF) and its mechanism. A mouse model of IPF was established by injection of bleomycin. C-MYC and miR-9-5p expression was determined by RT-qPCR and Western blot analysis. The interaction among C-MYC, miR-9-5p, and TBPL1 was detected by ChIP assay and dual luciferase reporter gene assay. After alteration of C-MYC, miR-9-5p, and TBPL1, their roles in pulmonary fibrosis and collagen fiber deposition in mice as well as proliferation and differentiation of pulmonary fibroblasts were assessed. Upregulated C-MYC expression was seen in the lung tissues of IPF mice and its silencing retarded IPF in mice. C-MYC could activate miR-9-5p that negatively regulated TBPL1 expression. Up-regulated C-MYC promoted proliferation and differentiation of pulmonary fibroblasts by inhibiting TBPL1 via activation of miR-9-5p, thus triggering IPF. Moreover, in the lung tissues-derived cells of IPF mice, C-MYC inhibitor, 10,058-F4, was observed to inhibit miR-9-5p expression, thereby repressing pulmonary fibrosis by up-regulating TBPL1. Our data provided evidence pinpointed the aggravative role of C-MYC in IPF by activating miR-9-5p to regulate TBPL1 expression. |
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MeSH term(s) | Animals ; Bleomycin/metabolism ; Bleomycin/pharmacology ; Cell Proliferation ; Fibroblasts/metabolism ; Idiopathic Pulmonary Fibrosis/genetics ; Idiopathic Pulmonary Fibrosis/metabolism ; Lung/metabolism ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; TATA Box Binding Protein-Like Proteins/metabolism |
Chemical Substances | MIRN9 microRNA, mouse ; MicroRNAs ; Myc protein, mouse ; Proto-Oncogene Proteins c-myc ; TATA Box Binding Protein-Like Proteins ; Tbpl1 protein, mouse ; Bleomycin (11056-06-7) |
Language | English |
Publishing date | 2022-02-03 |
Publishing country | England |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 1002702-6 |
ISSN | 1873-3913 ; 0898-6568 |
ISSN (online) | 1873-3913 |
ISSN | 0898-6568 |
DOI | 10.1016/j.cellsig.2022.110274 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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