Necrotizing Enterocolitis: LPS/TLR4-Induced Crosstalk Between Canonical TGF-β/Wnt/β-Catenin Pathways and PPARγ

Necrotizing enterocolitis (NEC) represents one of the major causes of morbidity and mortality in premature infants. Several recent studies, however, have contributed to a better understanding of the pathophysiology of this dreadful disease. Numerous intracellular pathways play a key role in NEC, namely: bacterial lipopolysaccharide (LPS), LPS toll-like receptor 4 (TLR4), canonical Wnt/beta-catenin signaling and PPAR gamma. In a large number of pathologies, canonical Wnt/beta-catenin signaling and PPAR gamma operate in opposition to one another, so that when one of the two pathways is overexpressed the other is downregulated and vice-versa. In NEC, activation of TLR4 by LPS leads to downregulation of the canonical Wnt/beta-catenin signaling and upregulation of PPAR gamma. This review aims to shed light on the complex intracellular mechanisms involved in this pathophysiological profile by examining additional pathways such as the GSK-3 beta, NF-kappa B, TGF-beta/Smads, and PI3K-Akt pathways.

Automated summary

NEC is a major cause of morbidity and mortality in premature infants. The pathophysiology of this disease involves multiple intracellular pathways such as Wnt/beta-catenin signaling, PPAR gamma, GSK-3 beta, NF-kappa B, TGF-beta/Smads, and PI3K-Akt pathways. Understanding these complex mechanisms is crucial for better management and treatment of NEC.