Biomedical Research Foundation Academy Of AthensAcademy Of Athens
Research Highlights :Coordinated activation of TGF-β and BMP pathways promotes autophagy and limits liver injury after acetaminophen intoxication

 

Paschalis Sideras, Athanasios Stavropoulos and colleagues recently published a study in Science Signaling

 

Balancing liver repair and regeneration

The related cytokines TGF-β and BMP exert protective or detrimental effects during liver injury, depending on the specific ligand and the type of injury. Stavropoulos et al. used mice expressing reporters for both TGF-β and BMP signaling to investigate the contributions of these pathways in the response to acetaminophen-induced liver injury. Both pathways were induced near areas of necrosis in hepatocytes that also showed an increase in autophagy. The TGF-β and BMP pathways cooperatively stimulated autophagy by promoting the expression of the gene encoding the rate-limiting autophagy factor Trp53inp2. Although inhibiting signaling through both pathways initially worsened acetaminophen-induced liver damage, it ultimately accelerated tissue regeneration and recovery. Transcriptomic analysis identified targets that were regulated in similar or opposite directions by the two pathways, highlighting the complexity of the interplay between these two signaling systems in liver injury and repair.

The paper has been selected to be featured on the current issue cover (volume 15, issue 740, 28 jun 2022)

 


pubmed

Coordinated activation of TGF-β and BMP pathways promotes autophagy and limits liver injury after acetaminophen intoxication
Stavropoulos A, Divolis G, Manioudaki M, Gavriil A, Kloukina I, Perrea DN, Sountoulidis A, Ford E, Doulou A, Apostolidou A, Katsantoni E, Ritvos O, Germanidis G, Xilouri M, Sideras P. Sci Signal. 2022 Jun 28;15(740):eabn4395. doi: 10.1126/scisignal.abn4395. Epub 2022 Jun 28. PMID: 35763560