Published online Jan 15, 2020. doi: 10.4251/wjgo.v12.i1.54
Peer-review started: June 4, 2019
First decision: July 31, 2019
Revised: August 5, 2019
Accepted: September 12, 2019
Article in press: September 12, 2019
Published online: January 15, 2020
Postoperative peritoneal adhesion (PPA), characterized by abdominal pain, female infertility, and even bowel obstruction after surgery, has always been a major concern. The occurrence and formation of adhesion are from complex biological processes. However, the molecular mechanisms underlying the basis of microarray data profile, followed by peritoneal adhesion formation, are largely unknown.
To reveal the underlying pathogenesis of PPA at the molecular level.
The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis. We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods. We performed quantitative PCR and western blotting in vivo to validate the results preliminarily.
In total, 446 expressed genes were altered in peritoneal adhesion. We found that several hub genes (e.g., tumor necrosis factor, interleukin 1 beta, interleukin 6, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2) were marked as significant biomarkers. Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway. According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies, TLR4, myeloid differentiation primary response protein 88 (MyD88), and nuclear factor kappa B (NF-κB) played essential roles in Toll-like signaling transduction. Here, we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion. The results of the microarray analysis were verified by the animal experiments. These findings may extend our understanding of the molecular mechanisms of PPA.
The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA. Future studies are required to validate our findings.
Core tip: Postoperative peritoneal adhesion remains an urgent clinical concern due to increasing abdominal surgery. The occurrence and formation of adhesion are from complex biological processes. However, the molecular mechanisms underlying the basis of microarray data profile, followed by peritoneal adhesion formation, are largely unknown. In this study, we uncovered the underlying pathogenesis of postoperative peritoneal adhesion at the molecular level using bioinformatics analysis methods. The results were further validated using animal experiments. It showed that the regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion played key roles in the pathogenesis of postoperative adhesion. Our findings may provide new insights into peritoneal adhesion formation.