Diabetic Csf1op/op Mice Lacking Macrophages Are Protected Against the Development of Delayed Gastric Emptying
| Autor: | Pieter Jan Verhulst, Joseph H. Szurszewski, Gianluca Cipriani, Tamas Ordog, Seth T. Eisenman, Gianrico Farrugia, Kyoung Moo Choi, Simon J. Gibbons, David R. Linden, Stephanie S. Hein |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
WT wild type Gastroparesis medicine.disease_cause Diabetic Complications chemistry.chemical_compound 0302 clinical medicine PCR polymerase chain reaction NDS normal donkey serum NS not statistically significant GE gastric emptying ANOVA analysis of variance Original Research Gastroenterology ICC interstitial cells of Cajal Malondialdehyde 3. Good health symbols Immunohistochemistry 030211 gastroenterology & hepatology medicine.drug Macrophage colony-stimulating factor medicine.medical_specialty PBS phosphate-buffered saline NOD nonobese diabetic 03 medical and health sciences symbols.namesake Diabetes mellitus Internal medicine HO1 heme-oxygenase 1 medicine lcsh:RC799-869 MDA malondialdehyde Csf1 macrophage colony stimulating factor Hepatology Gastric emptying business.industry Op osteopetrosis mutation medicine.disease Streptozotocin Interstitial Cells of Cajal Interstitial cell of Cajal 030104 developmental biology Endocrinology chemistry Immunology lcsh:Diseases of the digestive system. Gastroenterology business Oxidative stress qRT-PCR quantitative real-time reverse-transcription polymerase chain reaction |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology Cellular and Molecular Gastroenterology and Hepatology, Vol 2, Iss 1, Pp 40-47 (2016) |
| ISSN: | 2352-345X |
| Popis: | 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. Csf1op/op (Op/Op) mice lack biologically active Csf1 (macrophage colony stimulating factor), resulting in the absence of Csf1-dependent tissue macrophages. We used Csf1op/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: Csf1op/op mice had normal ICC. With onset of diabetes both Csf1op/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 Csf1op/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 Csf1op/op mice. Conclusions: Cellular injury and development of delayed GE 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 GE in diabetes. Keywords: Diabetic Complications, Gastroparesis, Interstitial Cells of Cajal |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|