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

Objective: We aimed to investigate whether inhibition of MUC1 would aggravate sepsis-induced ALI, and explore the predictive value of plasma MUC1 for sepsis patients with or without ARDS. Materials and methods: MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. Expression levels of MUC1, TLR 4 and HIF-1 alpha were detected by Western blot. In addition, plasma MUC1 levels of enrolled patients were detected by ELISA on the day of admission and on the 3rd day. ROC curve was used to determine the predictive value of MUC1 in sepsis patients with ARDS. Results: Our results showed that inhibition of MUC1 could aggravate sepsis-induced acute lung injury and increase the expression of inflammatory cytokines in sera and BALF of sepsis mice. At the same time, we confirmed that inhibition of MUC1 could significantly decrease HIF-1 alpha expression and thereby activate the expression level of TLR4. HIF-1 alpha was a negative regulator of TLR-4. In addition, plasma MUC1 levels of sepsis patients with ARDS were significantly higher than those without ARDS and healthy adults. ROC curve showed that predictive value of plasma MUC1 on sepsis with ARDS on the 3rd day of enrollment was higher than the day of enrollment. Conclusion: MUC1 could inhibit the expression of TLR-4 by stabilizing HIF-1 alpha, thereby alleviate sepsis-induced lung injury and protect organ function. At the same time, elevated MUC1 levels in plasma had a good predictive valud on whether patients with sepsis would develop ARDS.