Abstract | OBJECTIVE: METHODS: Lung sections of Fra-2 transgenic (n=12) and wild-type mice (n=6) were analysed at 16 weeks by histology using Dana Point criteria. Cellular and molecular key players were assessed by immunohistochemistry. To test the model's sensitivity to change over treatment, a subgroup of Fra-2 transgenic mice (n=6) was treated with the tyrosine kinase inhibitor nilotinib twice daily 37.5 mg orally from 8 weeks of age. RESULTS: CONCLUSIONS: This study suggests that Fra-2 transgenic mice as an animal model of systemic sclerosis-associated pulmonary arterial hypertension display main characteristic features of the human disease. It therefore allows studying pathophysiological aspects and might serve as a preclinical model for interventional proof-of-concept studies.
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Authors | Britta Maurer, Nicole Reich, Astrid Juengel, Jörg Kriegsmann, Renate E Gay, Georg Schett, Beat A Michel, Steffen Gay, Jörg H W Distler, Oliver Distler |
Journal | Annals of the rheumatic diseases
(Ann Rheum Dis)
Vol. 71
Issue 8
Pg. 1382-7
(Aug 2012)
ISSN: 1468-2060 [Electronic] England |
PMID | 22523431
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Fos-Related Antigen-2
- Fosl2 protein, mouse
- Pyrimidines
- Protein-Tyrosine Kinases
- nilotinib
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Topics |
- Animals
- Disease Models, Animal
- Enzyme Inhibitors
(pharmacology)
- Fos-Related Antigen-2
(genetics, metabolism)
- Hypertension, Pulmonary
(etiology, metabolism, pathology)
- Lung
(metabolism, pathology)
- Lung Diseases, Interstitial
(complications, drug therapy, pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Peripheral Vascular Diseases
(drug therapy, etiology, pathology)
- Protein-Tyrosine Kinases
(antagonists & inhibitors)
- Pulmonary Artery
(drug effects, pathology)
- Pulmonary Circulation
(drug effects)
- Pulmonary Fibrosis
(drug therapy, etiology, pathology)
- Pyrimidines
(pharmacology)
- Scleroderma, Systemic
(complications, metabolism, pathology)
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