Intestinal Adaptation upon Chemotherapy-Induced Intestinal Injury in Mice Depends on GLP-2 Receptor Activation
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Intestinal Adaptation upon Chemotherapy-Induced Intestinal Injury in Mice Depends on GLP-2 Receptor Activation. / Billeschou, Anna; Hunt, Jenna Elizabeth; Ghimire, Aruna; Holst, Jens J; Kissow, Hannelouise.
I: Biomedicines, Bind 9, Nr. 1, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Intestinal Adaptation upon Chemotherapy-Induced Intestinal Injury in Mice Depends on GLP-2 Receptor Activation
AU - Billeschou, Anna
AU - Hunt, Jenna Elizabeth
AU - Ghimire, Aruna
AU - Holst, Jens J
AU - Kissow, Hannelouise
PY - 2021
Y1 - 2021
N2 - Intestinal adaptation is an important response and a natural repair mechanism in acute intestinal injury and is critical for recovery. Glucagon-like peptide 2 (GLP-2) has been demonstrated to enhance mucosal repair following intestinal damage. In this study, we aimed to investigate the role of GLP-2 receptor activation on intestinal protection and adaptation upon chemotherapy-induced intestinal injury. The injury was induced with a single injection of 5-fluorouracil in female GLP-2 receptor knockout (GLP-2R(-/-)) mice and their wild type (WT) littermates. The mice were euthanized in the acute or the recovery phase of the injury; the small intestines were analysed for weight changes, morphology, histology, inflammation, apoptosis and proliferation. In the acute phase, only inflammation was slightly increased in the GLP-2R(-/-) mice compared to WT. In the recovery phase, we observed the natural compensatory response with an increase in small intestinal weight, crypt depth and villus height in WT mice, and this was absent in the GLP-2R(-/-) mice. Both genotypes responded with hyperproliferation. From this, we concluded that GLP-2R signalling does not have a major impact on acute intestinal injury but is pivotal for the adaptive response in the small intestine.
AB - Intestinal adaptation is an important response and a natural repair mechanism in acute intestinal injury and is critical for recovery. Glucagon-like peptide 2 (GLP-2) has been demonstrated to enhance mucosal repair following intestinal damage. In this study, we aimed to investigate the role of GLP-2 receptor activation on intestinal protection and adaptation upon chemotherapy-induced intestinal injury. The injury was induced with a single injection of 5-fluorouracil in female GLP-2 receptor knockout (GLP-2R(-/-)) mice and their wild type (WT) littermates. The mice were euthanized in the acute or the recovery phase of the injury; the small intestines were analysed for weight changes, morphology, histology, inflammation, apoptosis and proliferation. In the acute phase, only inflammation was slightly increased in the GLP-2R(-/-) mice compared to WT. In the recovery phase, we observed the natural compensatory response with an increase in small intestinal weight, crypt depth and villus height in WT mice, and this was absent in the GLP-2R(-/-) mice. Both genotypes responded with hyperproliferation. From this, we concluded that GLP-2R signalling does not have a major impact on acute intestinal injury but is pivotal for the adaptive response in the small intestine.
U2 - 10.3390/biomedicines9010046
DO - 10.3390/biomedicines9010046
M3 - Journal article
C2 - 33430185
VL - 9
JO - Biomedicines
JF - Biomedicines
SN - 2227-9059
IS - 1
ER -
ID: 255397555