摘要
BACKGROUND 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.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS 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.RESULTS 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,CX-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.CONCLUSION 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.
BACKGROUND 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.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS 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.RESULTS 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,CX-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(My D88),and nuclear factor kappa B(NF-κB) played essential roles in Toll-like signaling transduction.Here,we obtained a regulatory evidence chain of TLR4/My D88/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.CONCLUSION The regulatory evidence chain of TLR4/My D88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA.Future studies are required to validate our findings.
基金
Supported by the National Natural Science Foundation of China,No.81704084,No.81603529,and No.81673982
the Science and Technology Projects of Jiangsu Provincial Bureau of Traditional Chinese Medicine,No.YB2017002 and No.YB2015002
the Natural Science Foundation of the Jiangsu Higher Education Institutions,No.16KJB360002
the Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX18_1541
the Qing Lan Project
the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine(ZYX03KF63)
Jiangsu Government Scholarship for Overseas Studies and China Scholarship Council
