Deptor deficiency protects against acute lung injury through autophagy regulation
Year: 2026
Type: article
Abstract: Acute lung injury (ALI) is characterized by damage to alveolar epithelial and capillary endothelial cells, resulting in respiratory failure. The mTOR pathway plays a critical role in the progression of ALI, where its dysregulation leads to excessive autophagy activation and exacerbates cellular injury. Notably, Deptor has been identified as a key endogenous regulator of mTOR signaling. To investigate the role of Deptor in ALI pathogenesis, we used type II alveolar epithelial cell-specific Deptor knockout mice subjected to hemorrhagic shock and intratracheal lipopolysaccharide (LPS) instillation as an in vivo model, and employed LPS-stimulated MLE-12 cells for in vitro mechanistic exploration. Pathological changes, inflammatory responses, apoptosis, and key molecules of the mTOR signaling pathway and autophagy-related proteins were evaluated. Comparative analysis showed that Deptor knockout (Deptor⁻/⁻+ALI) mice exhibited significant alleviation of ALI-associated pathology. Deptor deletion markedly suppressed alveolar epithelial cell apoptosis and restored mTOR signaling. These protective effects were consistently observed in MLE-12 cells following Deptor knockdown. Furthermore, pharmacological inhibition of autophagy by 3‑MA reversed the detrimental effects of Deptor overexpression in LPS‑stimulated MLE-12 cells, reducing apoptosis and improving cell viability. Our study indicate that Deptor is upregulated in ALI and LPS‑stimulated cells, and that its elevation exacerbates injury via mTOR inhibition and autophagy hyperactivation, while its deficiency alleviates ALI by restoring mTOR signaling and limiting excessive autophagy. These results suggest Deptor as a potential therapeutic target for ALI.
Source: Scientific Reports
Institutions: Hangzhou Polytechnic, Tongde Hospital of Zhejiang Province, SUNY Upstate Medical University, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Sir Run Run Shaw Hospital, Zhejiang University, Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7225806664
FWCI:
Cites:
Cited by:
Related to: