Fig. 6: Blocking Rac2 signalling effectively reverses the human-like FBR induced by increased tissue-scale forces in mice.
Comparative analysis of histology sections of FBR capsules from the MSI mouse model either pharmacologically blocked with Rac inhibitor (RI) or genetically blocked in a Rac2−/− global KO mouse. a, Immunostaining for αSMA signalling in FBR capsules. Quantification of percent area positive for αSMA in each capsule (n = 5 biological replicates for each group; ***P = 0.0003). b, Trichrome staining of FBR capsules. Quantification of percent area positive for collagen in each capsule (n = 5 biological replicates for each group; *P = 0.045, **P = 0.0051). c, Haematoxylin and eosin (H&E) staining of FBR capsules. Quantification of average capsule thickness (n = 4 biological replicates for each group; *P = 0.0153). Scale bar in a–c, 50 µm. d, In SM implants, there is a modest activation of inflammatory pathways at the early time point, which subsides at the late time point, resulting in minimal FBR. In contrast, in MSI capsules, increased tissue-scale forces lead to the activation of Rac2 mechanical signalling, which promotes a robust activation of inflammatory markers that is sustained over time, resulting in a human-like pathological FBR. Statistical comparisons were made by using a one-way ANOVA with Tukey’s multiple comparisons tests. Each data point represents an independent capsule from a different mouse. All data represent mean ± s.e.m. Representative images are shown across all experiments. S, saline.
