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Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing

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@article{38202556e9f2432cb4268c0e8f8b1538,
title = "Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing",
abstract = "Background: The enteroendocrine hormone glucagon-like peptide- (GLP-) 2 is a potent trophic factor in the gastrointestinal tract. The GLP-2 receptor (GLP-2R) is expressed in the stroma of the large bowel wall, which is the major therapeutic target area to prevent anastomotic leakage. We investigated the efficacy of the long-acting GLP-2 analogue ZP1849 on colonic anastomotic wound healing.Methods: Eighty-seven male Wistar rats were stratified into four groups and received daily treatment with vehicle or ZP1849 starting one day before (day -1) end-to-end anastomosis was constructed in the left colon on day 0, and on days 0 (resected colon segment), 3, and 5, gene expressions of GLP-2R, Ki67, insulin-like growth factor- (IGF-) 1, type I (COL1A1) and type III (COL3A1) procollagens, cyclooxygenase- (COX-) 1, COX-2, and matrix metalloproteinase- (MMP-) 7 were quantified by RT-qPCR. Breaking strength, myeloperoxidase (MPO), transforming growth factor- (TGF-) β1, and soluble collagen proteins were measured on days 3 and 5.Results: ZP1849 treatment increased Ki67 (P < 0.0001) and IGF-1 (P < 0.05) mRNA levels in noninjured colon day 0, and postoperatively in the anastomotic wounds compared to vehicle-treated rats. ZP1849-treated rats had increased (P = 0.042) anastomotic breaking strength at day 5 compared with vehicle. COL1A1 and COL3A1 mRNA levels (P < 0.0001) and soluble collagen proteins (P < 0.05) increased from day 3 to day 5 in ZP1849-treated rats, but not in vehicle-treated rats. COX-2 mRNA and MPO protein levels decreased from day 3 to day 5 (P < 0.001) in both groups. ZP1849 treatment reduced TGF-β1 protein levels on day 5 (P < 0.001) but did not impact MMP-7 transcription.Conclusions: The GLP-2 analogue ZP1849 increased breaking strength, IGF-1 expression, and cell proliferation, which may be beneficial for colonic anastomotic wound healing.",
author = "Marie Kj{\ae}r and Wayne Russell and Peter Schjerling and Elena Cottarelli and Christjansen, {Kennet N} and Olsen, {Ditte M G} and Peter-Martin Krarup and Lene Jessen and Hansen, {Mark Berner} and J{\o}rgensen, {Lars Nannestad} and {\AA}gren, {Magnus S}",
note = "Copyright {\textcopyright} 2020 Marie Kjaer et al.",
year = "2020",
doi = "10.1155/2020/8460508",
language = "English",
volume = "2020",
pages = "8460508",
journal = "Gastroenterology Research and Practice",
issn = "1687-6121",
publisher = "Hindawi Publishing Corporation",

}

RIS

TY - JOUR

T1 - Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing

AU - Kjær, Marie

AU - Russell, Wayne

AU - Schjerling, Peter

AU - Cottarelli, Elena

AU - Christjansen, Kennet N

AU - Olsen, Ditte M G

AU - Krarup, Peter-Martin

AU - Jessen, Lene

AU - Hansen, Mark Berner

AU - Jørgensen, Lars Nannestad

AU - Ågren, Magnus S

N1 - Copyright © 2020 Marie Kjaer et al.

PY - 2020

Y1 - 2020

N2 - Background: The enteroendocrine hormone glucagon-like peptide- (GLP-) 2 is a potent trophic factor in the gastrointestinal tract. The GLP-2 receptor (GLP-2R) is expressed in the stroma of the large bowel wall, which is the major therapeutic target area to prevent anastomotic leakage. We investigated the efficacy of the long-acting GLP-2 analogue ZP1849 on colonic anastomotic wound healing.Methods: Eighty-seven male Wistar rats were stratified into four groups and received daily treatment with vehicle or ZP1849 starting one day before (day -1) end-to-end anastomosis was constructed in the left colon on day 0, and on days 0 (resected colon segment), 3, and 5, gene expressions of GLP-2R, Ki67, insulin-like growth factor- (IGF-) 1, type I (COL1A1) and type III (COL3A1) procollagens, cyclooxygenase- (COX-) 1, COX-2, and matrix metalloproteinase- (MMP-) 7 were quantified by RT-qPCR. Breaking strength, myeloperoxidase (MPO), transforming growth factor- (TGF-) β1, and soluble collagen proteins were measured on days 3 and 5.Results: ZP1849 treatment increased Ki67 (P < 0.0001) and IGF-1 (P < 0.05) mRNA levels in noninjured colon day 0, and postoperatively in the anastomotic wounds compared to vehicle-treated rats. ZP1849-treated rats had increased (P = 0.042) anastomotic breaking strength at day 5 compared with vehicle. COL1A1 and COL3A1 mRNA levels (P < 0.0001) and soluble collagen proteins (P < 0.05) increased from day 3 to day 5 in ZP1849-treated rats, but not in vehicle-treated rats. COX-2 mRNA and MPO protein levels decreased from day 3 to day 5 (P < 0.001) in both groups. ZP1849 treatment reduced TGF-β1 protein levels on day 5 (P < 0.001) but did not impact MMP-7 transcription.Conclusions: The GLP-2 analogue ZP1849 increased breaking strength, IGF-1 expression, and cell proliferation, which may be beneficial for colonic anastomotic wound healing.

AB - Background: The enteroendocrine hormone glucagon-like peptide- (GLP-) 2 is a potent trophic factor in the gastrointestinal tract. The GLP-2 receptor (GLP-2R) is expressed in the stroma of the large bowel wall, which is the major therapeutic target area to prevent anastomotic leakage. We investigated the efficacy of the long-acting GLP-2 analogue ZP1849 on colonic anastomotic wound healing.Methods: Eighty-seven male Wistar rats were stratified into four groups and received daily treatment with vehicle or ZP1849 starting one day before (day -1) end-to-end anastomosis was constructed in the left colon on day 0, and on days 0 (resected colon segment), 3, and 5, gene expressions of GLP-2R, Ki67, insulin-like growth factor- (IGF-) 1, type I (COL1A1) and type III (COL3A1) procollagens, cyclooxygenase- (COX-) 1, COX-2, and matrix metalloproteinase- (MMP-) 7 were quantified by RT-qPCR. Breaking strength, myeloperoxidase (MPO), transforming growth factor- (TGF-) β1, and soluble collagen proteins were measured on days 3 and 5.Results: ZP1849 treatment increased Ki67 (P < 0.0001) and IGF-1 (P < 0.05) mRNA levels in noninjured colon day 0, and postoperatively in the anastomotic wounds compared to vehicle-treated rats. ZP1849-treated rats had increased (P = 0.042) anastomotic breaking strength at day 5 compared with vehicle. COL1A1 and COL3A1 mRNA levels (P < 0.0001) and soluble collagen proteins (P < 0.05) increased from day 3 to day 5 in ZP1849-treated rats, but not in vehicle-treated rats. COX-2 mRNA and MPO protein levels decreased from day 3 to day 5 (P < 0.001) in both groups. ZP1849 treatment reduced TGF-β1 protein levels on day 5 (P < 0.001) but did not impact MMP-7 transcription.Conclusions: The GLP-2 analogue ZP1849 increased breaking strength, IGF-1 expression, and cell proliferation, which may be beneficial for colonic anastomotic wound healing.

U2 - 10.1155/2020/8460508

DO - 10.1155/2020/8460508

M3 - Journal article

C2 - 33133182

VL - 2020

SP - 8460508

JO - Gastroenterology Research and Practice

JF - Gastroenterology Research and Practice

SN - 1687-6121

ER -

ID: 61777508