Application of serum exosomal hypoxia-inducible factor-1 alpha (HIF-1α) as potential circulating biomarker for bacterial peritonitis

Bioengineered. 2022 Feb;13(2):1975-1987. doi: 10.1080/21655979.2021.2006866.

Abstract

Bacterial peritonitis is a severe disease that diagnosis remains challenging for clinicians. Measuring biomarkers might be a rapid diagnostic method. The objective of this study was to analyze and evaluate the dynamic changes in HIF-1α concentration in serum exosomes during bacterial peritonitis. The pre-clinical application value of serum exosomal HIF-1α was evaluated via imipenem and cilastatin sodium (ICS) intervention in the bacterial peritonitis model. The new colorimetric method to quantitate dynamic expression changes of HIF-1α in serum exosomes during bacterial peritonitis was established by our team via using the gold seed-coated with aptamer-functionalized Au @ Au core-shell peroxidase mimic. The typical inflammatory cytokines of bacterial peritonitis were also measured. Following intramuscular administration with ICS, In-Vivo Xtreme imaging system was used to visualize abdominal infection extent. Meanwhile, HIF-1α concentration in rat serum exosomes and pro-inflammatory factors levels in serum were detected. The serum typical inflammatory cytokines levels were elevated in GFP-labeled E.coli induced bacterial peritonitis. The serum exosomal HIF-1α levels clearly increased at 12 h, reached the peak during 24-48 h, and then gradually decreased at 72 h. Following intramuscular administration with ICS, the abdominal infection extent, HIF-1α concentration in serum exosomes, and the serum pro-inflammatory factors levels were reduced at 24 h in GFP-labeled E. coli induced bacterial peritonitis model. The serum exosomal HIF-1α can be used as a biomarker in the early stage of bacterial peritonitis, which might provide the basic research in the pre-clinical for further predicting and monitoring the pathological process of bacterial peritonitis.

Keywords: Bacterial peritonitis; HIF-1α; biomarker; exosome; hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Bacterial Infections / blood*
  • Biomarkers / blood
  • Female
  • Hypoxia-Inducible Factor 1, alpha Subunit / blood*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peritonitis / blood*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Biomarkers
  • Hif1a protein, mouse
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit

Grants and funding

This research was financially supported by the Macao Science and Technology Development Fund (0157/2019/A3 to Dr. Pei Luo). The content is solely the responsibility of the authors.