Fig. 4

Blockade of αv integrins by a small molecule (CWHM 12) attenuates established skeletal muscle and cardiac fibrosis, and αv integrins represent a tractable therapeutic target in human muscle fibrosis. a Dosing regime in the therapeutic skeletal muscle fibrosis model. Alzet osmotic minipumps containing CWHM 12 or CWHM 96 (control) were inserted ten days after intramuscular CTX injection. Tissues were harvested at day 21 following CTX injection. b Representative images of picrosirius red stained sections from control- and CWHM 12-treated mice. Scale bar 25 μm. c Digital image analysis quantification of collagen (picrosirius red staining) (n = 10). d Dosing regime in the therapeutic cardiac fibrosis model. Seven days following commencement of AngII treatment, Alzet osmotic minipumps containing CWHM 12 or CWHM 96 (control) were inserted. Tissues were harvested at day 14 after commencement of AngII treatment. e Representative images of picrosirius red stained sections from control- and CWHM 12-treated mice. Scale bars 1 mm in whole heart sections, 70 μm for magnified fields. f Digital image analysis quantification of collagen (picrosirius red staining) (n = 11). g, h Flow cytometric analysis of PDGFRβ and αv integrin expression on PDGFRβ⁺ cells from human skeletal muscle (g) and heart (h). i, j TGFβ activation by control- or CWHM 12-treated PDGRβ⁺ cells isolated from human skeletal muscle (i) and cardiac muscle (j) (n = 4). TGFβ activation was assessed alone, in the presence of TGFβ-blocking antibody (clone 1D11, 40 μg ml⁻¹) (anti-TGFβ), and in the presence of recombinant human TGFβ1 (rhTGFβ) (300 pg ml⁻¹). Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01 (Student’s t-test)