Acomys cahirinus develop lung stroma distortion but not fibrosis after bleomycin-induced injury
Nataliya A Basalova1,2, Vladimir S Popov1,2, Yulia G Antropova2
1Centre for Regenerative Medicine, Medical Research and Education Institute, Lomonosov Moscow State University, Moscow, 119234, Russia.
Background:
Spiny mice (Acomys sp.) have a unique ability of scarless regeneration. Therefore, the transfer of models used in convenient laboratory mice to study fibrosis could be a prospective approach, enabling the identification of novel antifibrotic therapies.
Methods:
In this study, we first applied a model of bleomycin-induced pulmonary fibrosis in Acomys cahirinus (Acomys), using Mus musculus C57BL/6 (Mus) as a control. Changes in lung tissue density were assessed using magnetic resonance imaging (MRI). The severity of fibrosis in lung tissue, as well as the deposition of extracellular matrix components, was assessed by histochemical analysis and morphometry (hematoxylin and eosin, Van Gieson). Data on the content of the main profibrotic proteins of the extracellular matrix, including collagen types I and IV, fibronectin, and fibronectin with EDA domain, were additionally validated by dot blotting. Changes in the number and localization of the main cell types contributing to the development of fibrosis (myofibroblasts, activated stromal cells, epithelium, M2 macrophages, leukocytes) were assessed by immunohistochemical analysis and morphometry. Statistical analysis was performed using GraphPad Prism software. Kruskal-Wallis H-test with the Dunn test and Mann-Whitney test was used for comparison between groups. Differences were considered significant when *p < 0.05.
Results:
Our data demonstrate that Acomys can survive high doses of bleomycin, which are sub-lethal and lethal for C57/Bl6 mice strain. In the head-to-head study, we performed an MRI to reveal changes in lung density as well as analyzed the morphology of Mus and Acomys lungs together with the identification of cell types required for fibrotic development. In contrast to Mus, Acomys demonstrated a decrease in respiratory regions upon bleomycin administration, but "classical" signs of fibrosis, such as fibrotic focuses or extracellular matrix accumulation, are detected only in small areas.
Conclusions:
The model of bleomycin-induced pulmonary fibrosis in Acomys is valid for the further investigation of possible mechanisms of resistance to damage-induced profibrotic stimuli.
