Diabetic Csf1(op/op) mice lacking macrophages are protected against the
development of delayed gastric emptying.
Authors Cipriani G, Gibbons SJ, Verhulst PJ, Choi KM, Eisenman ST, Hein SS, Ordog T,
Linden DR, Szurszewski JH, Farrugia G
Submitted By Gianrico Farrugia on 2/1/2016
Status Published
Journal Cellular and molecular gastroenterology and hepatology
Year 2016
Date Published 1/1/2016
Volume : Pages 2 : 40 - 47
PubMed Reference 26771000
Abstract Diabetic gastroparesis is associated with changes in interstitial cells of Cajal
(ICC), neurons and smooth muscle cells in both animal models and humans.
Macrophages appear to be critical to the development of cellular damage that
leads to delayed gastric emptying but the mechanisms involved are not well
understood. Csf1(op/op) (Op/Op) mice lack biologically active Csf1, resulting in
the absence of Csf1-dependent tissue macrophages. The aim of this study was to
use Csf1(op/op) mice to determine the role of macrophages in the development of
delayed gastric emptying., Animals were injected with streptozotocin to make
them diabetic. Gastric emptying was determined weekly. Immunohistochemistry was
used to identify macrophages and ICC networks in the gastric muscular layers.
Oxidative stress was measured by serum malondialdehyde (MDA) levels.
Quantitative, reverse transcription PCR was used to measure levels of mRNA.,
Csf1(op/op) mice had normal ICC. With onset of diabetes both Csf1(op/op) and
wild type Csf1(+/+) mice developed increased levels of oxidative stress (75.8 ±
9.1 and 41.2±13.6 nmol/mL MDA respectively). Wild type Csf1(+/+) mice developed
delayed gastric emptying after onset of diabetes (4/13) whereas no diabetic
Csf1(op/op) mouse developed delayed gastric emptying (0/15, P=0.035). ICC were
disrupted in diabetic wild type Csf1(+/+) mice with delayed gastric emptying but
remained normal in diabetic Csf1(op/op) mice., Cellular injury and development
of delayed gastric emptying in diabetes requires the presence of muscle layer
macrophages. Targeting macrophages may be an effective therapeutic option to
prevent cellular damage and development of delayed gastric emptying in diabetes.

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