Integrin β3 Mediates Sepsis and Mechanical Ventilation-Associated Pulmonary Fibrosis Through Glycometabolic...

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Biochemistry

Background:

• Mechanical ventilation (MV) is crucial for respiratory failure but its role in sepsis-associated pulmonary fibrosis is unclear.
• Sepsis and mechanical ventilation-associated pulmonary fibrosis (S-MVPF) is a complex condition requiring mechanistic understanding.
• Lung fibroblast activation is implicated in fibrotic processes.

Purpose of the Study:

• To investigate the mechanism of S-MVPF, focusing on integrin β3 activation.
• To explore the role of glycometabolic reprogramming in lung fibroblasts during S-MVPF.
• To determine if MV exacerbates lipopolysaccharide-induced pulmonary fibrosis.

Main Methods:

• Utilized a mouse model of lipopolysaccharide-induced sepsis and mechanical ventilation.
• Quantified fibroblast proliferation, collagen deposition, and procollagen type I carboxy-terminal propeptide.
• Assessed integrin β3, pyruvate kinase M2, lactate dehydrogenase A expression, and lactate levels.
• Employed integrin β3-knockout mice to evaluate its specific role.

Main Results:

• Mechanical ventilation aggravated sepsis-associated pulmonary fibrosis, increasing fibroblast proliferation and collagen deposition.
• Elevated integrin β3 and pyruvate kinase M2 expression, along with increased lactate dehydrogenase A and lactate, were observed in lung tissue.
• Integrin β3 knockout significantly attenuated S-MVPF and reduced associated molecular markers.
• Integrin β3 activation appears central to glycometabolic reprogramming in lung fibroblasts during S-MVPF.

Conclusions:

• Mechanical ventilation exacerbates sepsis-associated pulmonary fibrosis through integrin β3-mediated glycometabolic reprogramming of lung fibroblasts.
• Integrin β3 plays a critical role in the pathogenesis of S-MVPF.
• Targeting integrin β3-mediated metabolic pathways presents a potential therapeutic strategy for S-MVPF.