TPN-associated intestinal epithelial cell atrophy is modulated by TLR4/EGF signaling pathways

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Jennifer J FreemanDaniel H Teitelbaum

Abstract

Recent studies suggest a close interaction between epidermal growth factor (EGF) and TLR signaling in the modulation of intestinal epithelial cell (IEC) proliferation; however, how these signaling pathways adjust IEC proliferation is poorly understood. We utilized a model of total parenteral nutrition (TPN), or enteral nutrient deprivation, to study this interaction as TPN results in mucosal atrophy due to decreased IEC proliferation and increased apoptosis. We identified the novel finding of decreased mucosal atrophy in TLR4 knockout (TLR4KO) mice receiving TPN. We hypothesized that EGF signaling is preserved in TLR4KO-TPN mice and prevents mucosal atrophy. C57Bl/6 and strain-matched TLR4KO mice were provided either enteral feeding or TPN. IEC proliferation and apoptosis were measured. Cytokine and growth factor abundances were detected in both groups. To examine interdependence of these pathways, ErbB1 pharmacologic blockade was used. The marked decline in IEC proliferation with TPN was nearly prevented in TLR4KO mice, and intestinal length was partially preserved. EGF was significantly increased, and TNF-α decreased in TLR4KO-TPN versus wild-type (WT)-TPN mice. Apoptotic positive crypt cells were 15-fold higher in WT-TPN ver...Continue Reading

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Citations

Feb 20, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Jun-Kai YanTian Zhang
Oct 2, 2015·Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition·Farokh R DemehriDaniel H Teitelbaum
Dec 6, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jun-Kai YanYing Wang
Feb 7, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tian ZhangWei Cai
Jul 19, 2017·Annual Review of Nutrition·Hannah V Carey, Fariba M Assadi-Porter
Mar 21, 2018·Molecular and Cellular Biology·Hee Kyoung ChungJian-Ying Wang
Dec 25, 2019·Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition·Himani MadnawatAjay K Jain
Nov 18, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yang LiuWei Cai
Apr 1, 2021·American Journal of Physiology. Cell Physiology·Min S KwonJian-Ying Wang

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