Fig. 7: Tie2 inhibition rescued EC-pericyte associations with a therapeutic effect on CCM lesion progression. | Nature Communications

Fig. 7: Tie2 inhibition rescued EC-pericyte associations with a therapeutic effect on CCM lesion progression.

From: Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model

Fig. 7

a–h Short-term effects of Rebastinib on CCM lesions. a A diagram for the protocol. Vehicle or Rebastinib was subcutaneously injected into WT and P1 deletion Pdcd10BECKO mice, and brain tissues were harvested at P15. b Images of fresh brain tissue and H&E staining of brain sections. c Lesion quantifications from the H&E staining. n = 10. d Cerebellum sections were stained for CD31 with p-Tie2 or NG2, respectively. Representative images of normal vessels (arrowheads) and CCM lesions (asterisks) are shown captured by SP8 STED microscopy. e Quantification of p-Tie2 and NG2 coverage on CD31 vessels, n = 10. f–h Long-term effects of Rebastinib on CCM lesions. f A diagram for the protocol. Vehicle or Rebastinib was subcutaneously injected into WT and P1 deletion Pdcd10BECKO mice, and brain tissues were harvested at P60. g Images of fresh brain tissue and H&E staining of brain sections. i Lesion quantifications, n = 10. i–m Characterization of CCM lesions and EC-pericyte interactions by confocal microscopy. i A diagram for the protocol. Vehicle or Rebastinib was subcutaneously injected into WT and P5 deletion Pdcd10BECKO mice, and mice were analyzed at P60. j Two-month-old mice were perfused with a Texas Red IV dye and NeuroTrace (pericytes) followed by confocal microscopy. Representative images from each group are shown. Arrowheads indicate pericyte processes whereas arrows indicate pericytes dissociating from vessels. k Pericyte-free caverns were quantified. n = 4. l, m Characterization of CCM lesions and perfusion in WT (Mfsd2aCreERT2:mT/mG) and Pdcd10BECKO:mT/mG mice were visualized by confocal microscopy. l Representative images of normal or normalized microvessels (arrowheads) and CCM lesions (asterisks) are shown. Veins (V) and artery are indicated. m Vascular areas are quantified. n = 6. Data are means ± SEM. P values are indicated, one-way ANOVA followed by Tukey’s multiple comparisons test (c, e, h, k, m). Scale bars: 2 mm (upper panels in (b) and (g)); 25 μm (lower panels in (b) and (g)); 8 μm (d); 50 μm (j, l). Source data are provided as a Source data file.

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