CSE reduces OTUD4 triggering lung epithelial cell apoptosis via PAI-1 degradation

Area of Science:

• Molecular Biology
• Cell Biology
• Pulmonology

Background:

• Ovarian tumor deubiquitinase 4 (OTUD4) is a deubiquitinating enzyme linked to cancer cell apoptosis.
• The function of OTUD4 in cigarette smoke-induced airway epithelial cell apoptosis remains unclear.
• Cigarette smoke exposure is a major cause of lung diseases like emphysema.

Purpose of the Study:

• To investigate the role and mechanism of OTUD4 in cigarette smoke-induced epithelial cell apoptosis.
• To explore the potential therapeutic implications of the OTUD4/PAI-1 pathway in emphysema.

Main Methods:

• Western blotting to assess OTUD4 protein levels in mice and cells exposed to cigarette smoke extract (CSE).
• In vivo studies using mice with OTUD4 silence or restoration to evaluate lung tissue changes.
• In vitro experiments to confirm OTUD4's effect on apoptosis and its interaction with PAI-1.
• Protein interaction assays and deubiquitination analysis.

Main Results:

• OTUD4 protein levels were reduced in CSE-treated mice and airway epithelial cells.
• OTUD4 deficiency aggravated CSE-induced apoptosis and emphysema; OTUD4 restoration alleviated these effects.
• OTUD4 directly interacted with PAI-1, de-ubiquitinating and inhibiting CSE-induced PAI-1 degradation.
• PAI-1 inhibition blocked the protective effect of OTUD4 against apoptosis.

Conclusions:

• OTUD4 protects against cigarette smoke-induced airway epithelial cell apoptosis by modulating PAI-1 degradation.
• The OTUD4/PAI-1 signaling pathway is a potential therapeutic target for cigarette smoke-induced emphysema.