| First Author | Liu SS | Year | 2019 |
| Journal | Immunity | Volume | 51 |
| Issue | 3 | Pages | 522-534.e7 |
| PubMed ID | 31471107 | Mgi Jnum | J:282324 |
| Mgi Id | MGI:6380952 | Doi | 10.1016/j.immuni.2019.06.014 |
| Citation | Liu SS, et al. (2019) Targeting Degradation of the Transcription Factor C/EBPbeta Reduces Lung Fibrosis by Restoring Activity of the Ubiquitin-Editing Enzyme A20 in Macrophages. Immunity 51(3):522-534.e7 |
| abstractText | Although recent progress provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung epithelial injury results in injury-repairing response and inflammation, which drive the development of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing progressive accumulation of the transcription factor C/EBPbeta in alveolar macrophages (AMs) from PF patients and mice, which upregulated a number of immunosuppressive and profibrotic factors promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3beta (GSK-3beta) interacted with and phosphorylated A20 to suppress C/EBPbeta degradation. Ectopic expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3beta interaction accelerated C/EBPbeta degradation and showed potent therapeutic efficacy against experimental PF. Our study indicates that a regulatory mechanism of the GSK-3beta-A20-C/EBPbeta axis in AMs may be a potential target for treating PF and fibroproliferative lung diseases. |
