PLK1 protects intestinal barrier function in sepsis: A translational research

Cytokine. 2023 Feb:162:156113. doi: 10.1016/j.cyto.2022.156113. Epub 2022 Dec 21.

Abstract

Background: Sepsis and its related complications are very challenging in the intensive care unit, among which intestinal barrier injury is a general manifestation. Polo-like kinase 1 (PLK1) is widely studied in cancer, while its role in sepsis is poorly understood. In this study, the efficiency of PLK1 as a marker of intestinal barrier function as well as a predictor of mortality in sepsis was evaluated.

Methods: The level of serum PLK1 was measured in septic patients (n = 51) and controls (n = 20); subsequently, its correlation with serum diamine oxidase (DAO), d-lactate, and endotoxin levels and its ability topredict mortality were analysed. The survival rate and barrier injury degree were also assessed in septic mice.

Results: Serum PLK1 levels were elevated in septic patients, were negatively correlated with serum DAO, d-lactate, and endotoxin levels, and had a high predictive value for 28-day mortality in patients. The serum PLK1 level in non-survivors was lower. The expression of PLK1 in the intestine was decreased in septic mice, and overexpression or inhibition of PLK1 alleviated or aggravated intestinal barrier injury, respectively, as evaluated by Chiu's score, serum levels of DAO and d-lactate, and expression of tight junction proteins. Overexpressing PLK1 also decreased the 72-hour death rate of septic mice. Further study also revealed the negative correlation of PLK1 and IL-6 in patients, and increasing or interfering with PLK1 expression reduced or increased the serum IL-6 level in mice.

Conclusions: PLK1 plays a critical role in intestinal barrier function during sepsis, providing a novel perspective for sepsis therapy in the clinic.

Keywords: Interleukin-6; Intestinal barrier; Polo-like kinase 1; Sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endotoxins
  • Interleukin-6 / metabolism
  • Intestinal Mucosa* / metabolism
  • Lactic Acid
  • Mice
  • Polo-Like Kinase 1
  • Sepsis*
  • Translational Research, Biomedical

Substances

  • Endotoxins
  • Interleukin-6
  • Lactic Acid