Protective and predictive role of Mucin1 in sepsis-induced ALI/ARDS

Yu-Ming Wang1, Xing Qi1, Fang-Chen Gong1

  • 1Department of Emergency in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

Abstract

Insights

Inhibition of MUC1 worsens sepsis-induced acute lung injury. However, elevated plasma MUC1 levels predict acute respiratory distress syndrome (ARDS) in sepsis patients, offering diagnostic value.

Area of Science:

  • Biomedical research
  • Molecular biology
  • Critical care medicine

Background:

  • Mucin 1 (MUC1) is implicated in cellular processes.
  • Sepsis-induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions.
  • The role of MUC1 in sepsis-induced ALI and its predictive value for ARDS require clarification.

Purpose of the Study:

  • To investigate if MUC1 inhibition exacerbates sepsis-induced ALI.
  • To explore the predictive value of plasma MUC1 for sepsis patients with or without ARDS.

Main Methods:

  • MUC1 expression was inhibited using MUC1 siRNA in vitro and GO203 in vivo.
  • Western blot analysis detected MUC1, TLR4, and HIF-1α expression.
  • Plasma MUC1 levels were measured by ELISA in sepsis patients and healthy controls.
  • Receiver operating characteristic (ROC) curve analysis assessed MUC1's predictive value for ARDS.

Main Results:

  • MUC1 inhibition aggravated sepsis-induced ALI and increased inflammatory cytokines.
  • MUC1 inhibition decreased HIF-1α expression, leading to increased TLR4 activation.
  • Plasma MUC1 levels were significantly higher in sepsis patients with ARDS compared to those without and healthy adults.
  • Plasma MUC1 showed higher predictive value for ARDS on day 3 compared to day 1 of enrollment.

Conclusions:

  • MUC1 inhibits TLR-4 expression by stabilizing HIF-1α, alleviating sepsis-induced lung injury.
  • Elevated plasma MUC1 levels are a valuable predictor of ARDS development in sepsis patients.