کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5554525 1558871 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis
چکیده انگلیسی

Bleomycin (BLM) induced lung injury is detectable in C57BL/6 mice using magnetic resonance imaging (MRI). We investigated the effects of the fibroblast activation protein (FAP) inhibitor, PT100, in this model. BLM (0.5 mg/kg/day) was administered on days −7, −6, −5, −2, −1, 0 in the nostrils of male mice. PT100 (40 µg/mouse) or vehicle (0.9%NaCl) was dosed per os twice daily from day 1-14. MRI was performed before BLM and at days 0, 7 and 14. After the last MRI acquisition, animals were euthanised and the lungs harvested for histological and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. As evidenced longitudinally by MRI, the BLM-elicited lesions in the lungs of vehicle-treated mice progressed over time. In contrast, responses elicited by BLM did not progress in animals receiving PT100. Histology demonstrated significant less fibrosis in PT100- than in vehicle-treated, BLM-challenged mice. Significant correlation (R=0.91, P<0.001, N=24) was found between the volumes of BLM-induced lesions detected in vivo by MRI and the collagen content determined histologically (picrosirius staining). FAP was overexpressed in the lungs of BLM-challenged mice. Upon PT100 treatment, FAP expression was reduced. Significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs of PT100- compared to vehicle-treated mice were also revealed by qRT-PCR. The IBA-1 level determined histologically was higher in the lungs of PT100- compared to vehicle-treated mice. Taken together, these observations suggest that treatment with PT100 in this murine model of pulmonary fibrosis had an anti-fibro-proliferative effect and increased macrophage activation.

Lung MRI of spontaneously breathing mice to assess the effect of the fibroblast activation protein inhibitor, PT100. Axial multislice images through the chest of a saline-challenged, vehicle-treated animal and two bleomycin (BLM)-challenged mice, treated either with vehicle or PT100 from day 1 until the end of the study. Images were acquired at day 14 after last saline or BLM dosing. Vessels are indicated by white arrows, and BLM-induced lesions by red arrows.202

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 809, 15 August 2017, Pages 64-72
نویسندگان
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