The PLK1-mTOR Axis Regulates Autophagy to Prevent Intestinal Barrier Dysfunction During Sepsis

The intestines play a crucial role in the development of sepsis. The balance between autophagy and apoptosis in intestinal epithelial cells is dynamic and determines intestinal permeability. The present study focused on the potential role of autophagy in sepsis-induced intestinal barrier dysfunction and explored the mechanisms in vivo and in vitro. Excessive apoptosis in intestinal epithelia and a disrupted intestinal barrier were observed in septic mice. Promoting autophagy with rapamycin reduced intestinal epithelial apoptosis and restored intestinal barrier function, presenting as decreased serum DAO and FD40 levels and increased expression of ZO-1 and Occludin. PLK1 knockdown in mice ameliorated intestinal epithelial apoptosis and the intestinal barrier during sepsis, while these effects were reduced with chloroquine and enhanced with rapamycin. PLK1 also promotes cell autophagy and improves LPS-induced apoptosis and high permeability in vitro. Moreover, PLK1 physically interacted with mTOR and participated in reciprocal regulatory crosstalk in intestinal epithelial cells during sepsis. Our studies provide novel insight into the role of autophagy in sepsis-induced intestinal barrier dysfunction and indicate that the PLK1-mTOR axis may be a promising therapeutic target for sepsis.