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Hyaluronidase modulates bleomycin‐induced lung injury detected noninvasively in small rodents by radial proton MRI
Author(s) -
Egger Christine,
Cannet Catherine,
Gérard Christelle,
Dunbar Andrew,
Tigani Bruno,
Beckmann Nicolau
Publication year - 2015
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.24612
Subject(s) - hyaluronidase , bleomycin , hyaluronic acid , fibrosis , pathology , budesonide , medicine , magnetic resonance imaging , extracellular matrix , lung , chemistry , anatomy , radiology , biochemistry , corticosteroid , enzyme , chemotherapy
Purpose To assess whether hyaluronic acid, a building block of proteoglycans and extracellular matrix with hydrophilic characteristics, might contribute to magnetic resonance imaging (MRI)‐detected proton signals elicited by bleomycin in the lung. To this end, hyaluronidase, which degrades hyaluronic acid, was administered to bleomycin‐challenged animals. Materials and Methods Fibrosis was induced by oropharyngeal aspiration (OA) of bleomycin. Mice received bleomycin once daily (0.1 mg/kg) on 6 consecutive days, while rats were given a single dose (2 or 4 mg/kg). Hyaluronidase, budesonide, and the respective vehicles were also administered via OA. Animals were examined using a radial ultrashort echo time sequence. Histology of picrosirius reflecting collagen and tissue gene analysis were performed postmortem. Results In mice, hyaluronidase induced an increase of high intensity signals by 34 ± 12 μL (means ± SD, P = 0.007), consistent with the ability of the degradation products of hyaluronic acid to provoke acute inflammation. Budesonide was able to resolve hyaluronidase‐induced signals or to prevent their formation. Combined administration of budesonide and hyaluronidase to bleomycin‐treated rats resulted in an overall decrease (−17.1 ± 7%, P = 0.02) of the MRI‐detected bleomycin‐induced signals. Moreover, the relative gene expression of hyaluronidase was reduced (−61.8 ± 10.2%, P < 0.001) in fibrotic lungs. Conclusion The present data indicate that hyaluronic acid contributes to the bleomycin‐induced responses detected by MRI in the lung. J. Magn. Reson. Imaging 2015;41:755–764. © 2014 Wiley Periodicals, Inc.