The Role of NF-κB in Peritoneal Fibrosis and Adhesion in Humans and Animals: A Systematic Review

TL;DR

This paper reviews how the NF-κB pathway contributes to peritoneal fibrosis and adhesions, and how targeting it may help prevent complications in dialysis patients.

Contribution

A systematic review compiling 39 studies on NF-κB's role in peritoneal fibrosis and adhesions, highlighting its activation and therapeutic inhibition.

Findings

NF-κB activation is linked to peritoneal fibrosis and adhesions in human and animal studies.

Inhibiting NF-κB activity reduces inflammatory and fibrotic markers in both fibrosis and adhesion models.

Most therapeutic studies showed benefits from targeting NF-κB in managing peritoneal complications.

Abstract

Peritoneal fibrosis is a consequence of peritoneal dialysis, initiated by an inflammatory response in the peritoneum, whereas peritoneal adhesions represent intra-abdominal post-inflammatory complications. Given that the nuclear factor kappa B (NF-κB) signaling pathway plays a central role in inflammation, this systematic review aims to compile research findings on the role of NF-κB in peritoneal fibrosis and adhesions. Following the PRISMA 2020 guidelines, literature searches were conducted in PubMed, Scopus, and Web of Knowledge. Inclusion criteria covered research articles investigating NF-κB in peritoneal fibrosis and adhesions. Selected studies were categorized based on NF-κB-mediated regulation and NF-κB-targeted therapies. To date, the role of NF-κB in peritoneal fibrosis and adhesions has been described in 39 publications: 29 on fibrosis, 9 on adhesions, and 1 addressing both conditions. NF-κB activation was reported in human and animal studies, both in vitro and in vivo, in response to stimuli such as high glucose, inflammatory cytokines, growth factor, bacteria, and irritants. This activation led to upregulation of specific inflammatory, mesothelial-to-mesenchymal transition, fibrosis, and angiogenesis markers. All 21 therapeutic studies demonstrated inhibition of NF-κB activity and downregulation of related molecular markers—15 in fibrosis and 6 in adhesions. Controlling NF-κB activity in the peritoneal mesothelium may be beneficial in managing peritoneal dialysis and preventing peritoneal post-inflammatory complications.

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