Diabetic Csf1op/op Mice Lacking Macrophages Are Protected Against the Development of Delayed Gastric Emptying

作者：Gianluca Cipriani, Simon J. Gibbons, Pieter-Jan Verhulst, Kyoung Moo Choi, Seth T. Eisenman, Stephanie Hein, Tamás Ördög, David R. Linden, Joseph H. Szurszewski, Gianrico Farrugia · 发表于：Cellular and Molecular Gastroenterology and Hepatology · 年份：2015 · DOI：10.1016/j.jcmgh.2015.09.001 · 被引用次数：50 · 研究领域：Gastrointestinal motility and disorders、Dietary Effects on Health、IL-33, ST2, and ILC Pathways

Background & Aims 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 (GE), but the mechanisms involved are not well understood. Csf1 op/op (Op/Op) mice lack biologically active Csf1 (macrophage colony stimulating factor), resulting in the absence of Csf1-dependent tissue macrophages. We used Csf1 op/op mice to determine the role of macrophages in the development of delayed GE. Methods Animals were injected with streptozotocin to make them diabetic. GE 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 polymerase chain reaction was used to measure levels of mRNA. Results 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 GE after the onset of diabetes (4 of 13) whereas no diabetic Csf1 op/op mouse developed delayed GE (0 of 15, P = .035). The ICC were disrupted in diabetic wild-type Csf1 +/+ mice with delayed GE but remained normal in diabetic Csf1 op/op mice. Conclusions Cellular injury and developme...