Fig. 5

Fibronectin expressed by reactive astrocytes is associated with intercellular interaction between astrocytes and microglia in vivo. a Peri-lesional glial scar of the chronically injured spinal cord. Asterisk indicates the lesion epicenter. GFAP, red; Fibronectin, green; TMEM119, white. Scale bar, 200 μm. b Magnification of inset b in a. GFAP, red; Fibronectin, green. Scale bar, 100 μm. c Magnification of inset c in a. CD11b, white; Fibronectin, green. Scale bar, 100 μm. d The administration of anti-β1 integrin antibody had no effect on the mRNA expression of Fn1 within glial scars. The error bar indicates mean ± SEM. Star indicates statistical significance (p < 0.05). n.s., not significant. Wilcoxon’s rank-sum test. n = 4 per each group, duplicate. F = 0.192. e The TNFα mRNA expression of BV-2 cells after fibronectin stimulation with or without β1Ab pre-treatment. Error bar indicates mean ± SEM. Star indicates statistical significance (p < 0.05). Wilcoxon’s rank-sum test. n = 3 per each group, triplicate. f Our hypothesis of the novel glial scar pathology and therapeutic effects of anti-β1 integrin antibody. Fibronectin is suggested to be expressed by reactive astrocytes and recognized by the β1 integrin receptor in microglia. Microglia attain a pro-inflammatory phenotype by fibronectin. As previously reported, the antibody blocked the interaction between reactive astrocytes and collagen, leading to the suppression of glial scar formation. The present findings suggested that the antibody also blocked interaction between reactive astrocytes and fibronectin, leading to microglia polarization within the glial scar to an anti-inflammatory condition. These integrated effects of anti-β1 integrin antibody administration can modulate the glial scar pathology and improve the chronic microenvironment after SCI