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

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  • 作者:Shuya Mei, Ri Tang, Yue Hu, Jinhua Feng, Qiaoyi Xu, Yang Zhou, Han Zhong, Yuan Gao, Zhengyu He, Shunpeng Xing
  • 期刊:LABORATORY INVESTIGATION
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Mechanical ventilation (MV) has become a clinical first-line treatment option for patients with respiratory failure. However, it was unclear whether MV further aggravates the process of sepsis-associated pulmonary fibrosis and eventually leads to sepsis and mechanical ventilation-associated pulmonary fibrosis (S-MVPF). This study aimed to explore the mechanism of S-MVPF concerning integrin β3 activation in glycometabolic reprogramming of lung fibroblasts. We found that MV exacerbated sepsis-associated pulmonary fibrosis induced by lipopolysaccharide, which was accompanied by proliferation of lung fibroblasts, increased deposition of collagen in lung tissue, and increased procollagen type I carboxy-terminal propeptide in the bronchoalveolar lavage fluid. A large number of integrin β3- and pyruvate kinase M2-positive fibroblasts were detected in lung tissue after stimulation with lipopolysaccharide and MV, with an increase in lactate dehydrogenase A expression and lactate levels. S-MVPF was primarily attenuated in integrin β3-knockout mice, which also resulted in a decrease in the levels of pyruvate kinase M2, lactate dehydrogenase A, and lactate. In conclusion, MV aggravated sepsis-associated pulmonary fibrosis, with glycometabolic reprogramming mediated by integrin β3 activation. Thus, integrin β3-mediated glycometabolic reprogramming might be a potential therapeutic target for S-MVPF.

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