Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition

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Standard

Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition. / Feng, Yongjia; Demehri, Farok R; Xiao, Weidong; Tsai, Yu-Hwai; Jones, Jennifer C; Brindley, Constance D; Threadgill, David W; Holst, Jens J; Hartmann, Bolette; Barrett, Terrence A; Teitelbaum, Daniel H; Dempsey, Peter J.

I: Cellular and molecular gastroenterology and hepatology, Bind 3, Nr. 3, 05.2017, s. 447-468.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Feng, Y, Demehri, FR, Xiao, W, Tsai, Y-H, Jones, JC, Brindley, CD, Threadgill, DW, Holst, JJ, Hartmann, B, Barrett, TA, Teitelbaum, DH & Dempsey, PJ 2017, 'Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition', Cellular and molecular gastroenterology and hepatology, bind 3, nr. 3, s. 447-468. https://doi.org/10.1016/j.jcmgh.2016.12.005

APA

Feng, Y., Demehri, F. R., Xiao, W., Tsai, Y-H., Jones, J. C., Brindley, C. D., ... Dempsey, P. J. (2017). Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition. Cellular and molecular gastroenterology and hepatology, 3(3), 447-468. https://doi.org/10.1016/j.jcmgh.2016.12.005

Vancouver

Feng Y, Demehri FR, Xiao W, Tsai Y-H, Jones JC, Brindley CD o.a. Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition. Cellular and molecular gastroenterology and hepatology. 2017 maj;3(3):447-468. https://doi.org/10.1016/j.jcmgh.2016.12.005

Author

Feng, Yongjia ; Demehri, Farok R ; Xiao, Weidong ; Tsai, Yu-Hwai ; Jones, Jennifer C ; Brindley, Constance D ; Threadgill, David W ; Holst, Jens J ; Hartmann, Bolette ; Barrett, Terrence A ; Teitelbaum, Daniel H ; Dempsey, Peter J. / Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition. I: Cellular and molecular gastroenterology and hepatology. 2017 ; Bind 3, Nr. 3. s. 447-468.

Bibtex

@article{92f8379862444ced9958df680c778774,
title = "Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition",
abstract = "BACKGROUND & AIMS: Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal epithelial cell (IEC) responses and attenuate mucosal atrophy in several TPN models. However, it remains unclear whether these 2 factors use distinct or overlapping signaling pathways to improve IEC responses. We investigated the interaction of GLP-2 and EGF signaling in a mouse TPN model and in patients deprived of enteral nutrition.METHODS: Adult C57BL/6J, IEC-Egfr(knock out (KO)) and IEC-pik3r1(KO) mice receiving TPN or enteral nutrition were treated with EGF or GLP-2 alone or in combination with reciprocal receptor inhibitors, GLP-2(3-33) or gefitinib. Jejunum was collected and mucosal atrophy and IEC responses were assessed by histologic, gene, and protein expression analyses. In patients undergoing planned looped ileostomies, fed and unfed ileum was analyzed.RESULTS: Enteral nutrient deprivation reduced endogenous EGF and GLP-2 signaling in mice and human beings. In the mouse TPN model, exogenous EGF or GLP-2 attenuated mucosal atrophy and restored IEC proliferation. The beneficial effects of EGF and GLP-2 were decreased upon Gefitinib treatment and in TPN-treated IEC-Egfr(KO) mice, showing epidermal growth factor-receptor dependency for these IEC responses. By contrast, in TPN-treated IEC-pi3kr1(KO) mice, the beneficial actions of EGF were lost, although GLP-2 still attenuated mucosal atrophy.CONCLUSIONS: Upon enteral nutrient deprivation, exogenous GLP-2 and EGF show strong interdependency for improving IEC responses. Understanding the differential requirements for phosphatidylinositol 3-kinase/phosphoAKT (Ser473) signaling may help improve future therapies to prevent mucosal atrophy.",
keywords = "Journal Article",
author = "Yongjia Feng and Demehri, {Farok R} and Weidong Xiao and Yu-Hwai Tsai and Jones, {Jennifer C} and Brindley, {Constance D} and Threadgill, {David W} and Holst, {Jens J} and Bolette Hartmann and Barrett, {Terrence A} and Teitelbaum, {Daniel H} and Dempsey, {Peter J}",
year = "2017",
month = "5",
doi = "10.1016/j.jcmgh.2016.12.005",
language = "English",
volume = "3",
pages = "447--468",
journal = "Cellular and Molecular Gastroenterology and Hepatology",
issn = "2352-345X",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition

AU - Feng, Yongjia

AU - Demehri, Farok R

AU - Xiao, Weidong

AU - Tsai, Yu-Hwai

AU - Jones, Jennifer C

AU - Brindley, Constance D

AU - Threadgill, David W

AU - Holst, Jens J

AU - Hartmann, Bolette

AU - Barrett, Terrence A

AU - Teitelbaum, Daniel H

AU - Dempsey, Peter J

PY - 2017/5

Y1 - 2017/5

N2 - BACKGROUND & AIMS: Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal epithelial cell (IEC) responses and attenuate mucosal atrophy in several TPN models. However, it remains unclear whether these 2 factors use distinct or overlapping signaling pathways to improve IEC responses. We investigated the interaction of GLP-2 and EGF signaling in a mouse TPN model and in patients deprived of enteral nutrition.METHODS: Adult C57BL/6J, IEC-Egfr(knock out (KO)) and IEC-pik3r1(KO) mice receiving TPN or enteral nutrition were treated with EGF or GLP-2 alone or in combination with reciprocal receptor inhibitors, GLP-2(3-33) or gefitinib. Jejunum was collected and mucosal atrophy and IEC responses were assessed by histologic, gene, and protein expression analyses. In patients undergoing planned looped ileostomies, fed and unfed ileum was analyzed.RESULTS: Enteral nutrient deprivation reduced endogenous EGF and GLP-2 signaling in mice and human beings. In the mouse TPN model, exogenous EGF or GLP-2 attenuated mucosal atrophy and restored IEC proliferation. The beneficial effects of EGF and GLP-2 were decreased upon Gefitinib treatment and in TPN-treated IEC-Egfr(KO) mice, showing epidermal growth factor-receptor dependency for these IEC responses. By contrast, in TPN-treated IEC-pi3kr1(KO) mice, the beneficial actions of EGF were lost, although GLP-2 still attenuated mucosal atrophy.CONCLUSIONS: Upon enteral nutrient deprivation, exogenous GLP-2 and EGF show strong interdependency for improving IEC responses. Understanding the differential requirements for phosphatidylinositol 3-kinase/phosphoAKT (Ser473) signaling may help improve future therapies to prevent mucosal atrophy.

AB - BACKGROUND & AIMS: Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal epithelial cell (IEC) responses and attenuate mucosal atrophy in several TPN models. However, it remains unclear whether these 2 factors use distinct or overlapping signaling pathways to improve IEC responses. We investigated the interaction of GLP-2 and EGF signaling in a mouse TPN model and in patients deprived of enteral nutrition.METHODS: Adult C57BL/6J, IEC-Egfr(knock out (KO)) and IEC-pik3r1(KO) mice receiving TPN or enteral nutrition were treated with EGF or GLP-2 alone or in combination with reciprocal receptor inhibitors, GLP-2(3-33) or gefitinib. Jejunum was collected and mucosal atrophy and IEC responses were assessed by histologic, gene, and protein expression analyses. In patients undergoing planned looped ileostomies, fed and unfed ileum was analyzed.RESULTS: Enteral nutrient deprivation reduced endogenous EGF and GLP-2 signaling in mice and human beings. In the mouse TPN model, exogenous EGF or GLP-2 attenuated mucosal atrophy and restored IEC proliferation. The beneficial effects of EGF and GLP-2 were decreased upon Gefitinib treatment and in TPN-treated IEC-Egfr(KO) mice, showing epidermal growth factor-receptor dependency for these IEC responses. By contrast, in TPN-treated IEC-pi3kr1(KO) mice, the beneficial actions of EGF were lost, although GLP-2 still attenuated mucosal atrophy.CONCLUSIONS: Upon enteral nutrient deprivation, exogenous GLP-2 and EGF show strong interdependency for improving IEC responses. Understanding the differential requirements for phosphatidylinositol 3-kinase/phosphoAKT (Ser473) signaling may help improve future therapies to prevent mucosal atrophy.

KW - Journal Article

U2 - 10.1016/j.jcmgh.2016.12.005

DO - 10.1016/j.jcmgh.2016.12.005

M3 - Journal article

C2 - 28462383

VL - 3

SP - 447

EP - 468

JO - Cellular and Molecular Gastroenterology and Hepatology

JF - Cellular and Molecular Gastroenterology and Hepatology

SN - 2352-345X

IS - 3

ER -

ID: 182972569