Journal article
Hyaluronidase modulates bleomycin-induced lung injury detected noninvasively in small rodents by radial proton MRI.
- Egger C Novartis Institutes for BioMedical Research, Analytical Sciences and Imaging, Basel, Switzerland; University of Basel, Biocenter, Basel, Switzerland.
- Cannet C
- Gérard C
- Dunbar A
- Tigani B
- Beckmann N
- 2014-03-14
Published in:
- Journal of magnetic resonance imaging : JMRI. - 2015
bleomycin
fibrosis
hyaluronic acid (hyaluronan)
lung
magnetic resonance imaging (MRI)
ultrashort echo time (UTE)
Analysis of Variance
Animals
Bleomycin
Disease Models, Animal
Fibrosis
Hyaluronoglucosaminidase
Lung
Lung Injury
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred C57BL
Protons
Rats
Rats, Sprague-Dawley
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1002/jmri.24612
- PMID 24623374
- Persistent URL
- https://sonar.ch/global/documents/238150
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