Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing
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...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2020/8460508 |
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| author | Marie Kjaer Wayne Russell Peter Schjerling Elena Cottarelli Kennet N. Christjansen Ditte M. G. Olsen Peter-Martin Krarup Lene Jessen Mark Berner-Hansen Lars N. Jorgensen Magnus S. Ågren |
| author_facet | Marie Kjaer Wayne Russell Peter Schjerling Elena Cottarelli Kennet N. Christjansen Ditte M. G. Olsen Peter-Martin Krarup Lene Jessen Mark Berner-Hansen Lars N. Jorgensen Magnus S. Ågren |
| author_sort | Marie Kjaer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3941f570c9da470fb31cf22360242260 |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-3941f570c9da470fb31cf223602422602025-02-03T01:28:24ZengWileyGastroenterology Research and Practice1687-61211687-630X2020-01-01202010.1155/2020/84605088460508Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound HealingMarie Kjaer0Wayne Russell1Peter Schjerling2Elena Cottarelli3Kennet N. Christjansen4Ditte M. G. Olsen5Peter-Martin Krarup6Lene Jessen7Mark Berner-Hansen8Lars N. Jorgensen9Magnus S. Ågren10Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen NV, DenmarkZealand Pharma A/S, 2600 Glostrup, DenmarkInstitute of Sports Medicine Copenhagen and Department of Biomedical Sciences, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen NV, DenmarkDigestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen NV, DenmarkZealand Pharma A/S, 2600 Glostrup, DenmarkZealand Pharma A/S, 2600 Glostrup, DenmarkDigestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen NV, DenmarkZealand Pharma A/S, 2600 Glostrup, DenmarkDigestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen NV, DenmarkDigestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen NV, DenmarkDigestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen NV, DenmarkBackground. 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.http://dx.doi.org/10.1155/2020/8460508 |
| spellingShingle | Marie Kjaer Wayne Russell Peter Schjerling Elena Cottarelli Kennet N. Christjansen Ditte M. G. Olsen Peter-Martin Krarup Lene Jessen Mark Berner-Hansen Lars N. Jorgensen Magnus S. Ågren Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing Gastroenterology Research and Practice |
| title | Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing |
| title_full | Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing |
| title_fullStr | Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing |
| title_full_unstemmed | Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing |
| title_short | Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing |
| title_sort | glucagon like peptide 2 analogue zp1849 augments colonic anastomotic wound healing |
| url | http://dx.doi.org/10.1155/2020/8460508 |
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