Organizing pneumonia in mice and men
| Autor: | Gregor Warnecke, Nicole Izykowski, Kristin Mitschke, Florian Laenger, Ulrich A. Maus, Axel Haverich, Kais Hussein, Danny Jonigk, Sabina Janciauskiene, Michael D. Gunn, Mark Kuehnel |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Pathology medicine.medical_specialty MMP2 Mice Transgenic General Biochemistry Genetics and Molecular Biology Pathogenesis 03 medical and health sciences 0302 clinical medicine Laser-assisted microdissection Animals Humans Medicine CCL2 transgenic mouse RNA Messenger Lung Chemokine CCL2 Microdissection Organizing pneumonia TIMP1 Medicine(all) Biochemistry Genetics and Molecular Biology(all) business.industry Research Pneumonia General Medicine Gene expression profiling 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Immunology Immunohistochemistry business Signal Transduction |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| Popis: | Background Organizing pneumonia is a reaction pattern and an inflammatory response to acute lung injuries, and is characterized by intraluminal plugs of granulation tissue in distal airspaces. In contrast to other fibrotic pulmonary diseases, organizing pneumonia is generally responsive to corticosteroids. However, some patients do not respond to treatment, leading to respiratory failure and potentially death (up to 15 % of patients). In order to devise new therapeutic strategies, a better understanding of the disease’s pathomechanisms is warranted. We previously generated a mouse model overexpressing CCL2, which generates organizing pneumonia-like changes, morphologically comparable to human patients. In this study, we investigated whether the histopathological similarities of human and murine pulmonary organizing pneumonia lesions also involve similar molecular pathways. Methods We analyzed the similarities and differences of fibrosis-associated gene expression in individual compartments from patients with organizing pneumonia and transgenic (CCL2) mice using laser-assisted microdissection, real-time PCR and immunohistochemistry. Results Gene expression profiling of human and murine organizing pneumonia lesions showed in part comparable expression levels of pivotal genes, notably of TGFB1/Tgfb1, TIMP1/Timp1, TIMP2/Timp2, COL3A1/Col3a1, CXCL12/Cxcl12, MMP2/Mmp2 and IL6/Il6. Hence, the transgenic CCL2 mouse model shows not only pathogenomic and morphological features of human organizing pneumonia but also a similar inflammatory profile. Conclusions We suggest that the CCL2-overexpressing transgenic mouse model (CCL2 Tg mice) is suitable for further investigation of fibrotic pulmonary remodeling, particularly of organizing pneumonia pathogenesis and for the search for novel therapeutic strategies. |
| Databáze: | OpenAIRE |
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