1. The Ying and Yang of Bacterial Signaling in Necrotizing Enterocolitis
María T. Abreu 
Gastroenterology 
Volume 138, Issue 1, Pages (January 2010)
DOI: /j.gastro
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2. Figure 1
Intestinal epithelial cells in the proliferative state integrate a variety of growth signals. Wnts are proteins that interact with the receptor frizzled (Fzd) and its co-receptor LRP. Once activated, disheveled (Dsh) phosphorylates glycogen synthase kinase 3 β leading to its decreased function. By decreasing its function, less β-catenin is phosphorylated. When β-catenin is phosphorylated, it is targeted for ubiquitination and proteosomal degradation. In the presence of Wnt, less β-catenin is degraded and is then available to enter the nucleus where it binds the Tcf transcription factor leading to expression of genes involved in proliferation including cyclin D1. On the left is a model of what occurs in the NEC-susceptible intestine. Whereas normal infant intestinal epithelial cells express low levels of TLR4 (or have decreased downstream signaling), prematurity, formula feeding, and hypoxia result in increased TLR4 expression through unknown mechanisms. TLR4 inhibits Akt phosphorylation. Akt phosphorylates and inactivates GSK3β. By inhibiting Akt phosphorylation, GSK3β remains in its active state and phosphorylates β-catenin leading to its degradation. Hackam and colleagues show that expression of active β-catenin can bypass the inhibition of proliferation caused by LPS in the NEC intestine.
Gastroenterology  , 39-43DOI: ( /j.gastro )
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