Premium
Dissociation of E‐cadherin and β‐catenin in a mouse model of total parenteral nutrition: a mechanism for the loss of epithelial cell proliferation and villus atrophy
Author(s) -
Feng Yongjia,
Sun Xiaoyi,
Yang Hua,
Teitelbaum Daniel H.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.162719
Subject(s) - catenin , parenteral nutrition , cyclin d1 , cell growth , pi3k/akt/mtor pathway , cadherin , medicine , endocrinology , intracellular , phosphorylation , biology , beta catenin , cancer research , microbiology and biotechnology , apoptosis , signal transduction , cell , wnt signaling pathway , cell cycle , biochemistry
Total parenteral nutrition (TPN) leads a loss of epithelial barrier function, decline in epithelial cell (EC) proliferation, and decreased expression of E‐cadherin. As a large portion of intracellular β‐catenin is tightly associated with E‐cadherin, we hypothesized that the loss of E‐cadherin would result in a redistribution of intracellular β‐catenin, and could be a contributing mechanism for this TPN‐associated loss of EC proliferation. An assessment of small bowel epithelium was performed in mice given either enteral nutrition (Control) or intravenous nutrition (TPN). TPN significantly down‐regulated E‐cadherin and β‐catenin expression, and resulted in a loss of a colocalization of these factors. TPN also up‐regulated phosphorylated (p)‐β‐catenin (Ser31/33,Thr41) and down‐regulated (p)‐β‐catenin(Ser552) expression. To further address mechanisms driving this, we observed a significant decrease in the abundance of p‐AKT and p‐GSK3β expression, and an associated decline in tcf‐4 transcription factors (cyclin D1, c‐myc and Axin2), as well as a loss of EC proliferation by 7 days. To address whether the mechanism driving these changes was the absence of nutritional factors, glutamine was added to the TPN solution. This resulted in a partial restoration of β‐catenin expression and EC proliferation, suggesting that an alteration in nutrient delivery may affect many of these changes. Based on these findings, the loss of EC proliferation with TPN may well be due to a loss of total β‐catenin, as well as a concomintant change in the differential expression of β‐catenin phosphorylation sites, and a reduction in β‐catenin mediated tcf‐4 transcription. This potential pathway may well explain many of the findings of mucosal atrophy associated with TPN.