Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis

Egger, Christine and Cannet, Catherine and Gerard Sachot, Christelle and Pierrat, Benoit and Suply, Thomas and Ksiazek, Iwona and Beckmann, Nicolau (2017) Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. European Journal of Pharmacology, 809. pp. 64-72. ISSN 18790712

Abstract

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.

Item Type: Article
Keywords: Bleomycin (BLM) Fibroblast activation protein (FAP) Fibrosis Lung Magnetic resonance imaging (MRI) PT100
Date Deposited: 29 Nov 2017 00:45
Last Modified: 25 Jan 2019 00:46
URI: https://oak.novartis.com/id/eprint/10537

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.