Figure 3
Figure 3. Aberrant mural cell recruitment results in perilymphatic accumulation of hyaluronan with subsequent formation of fibrotic lesions. (A) Simultaneous immunodetection of HA and lymphatic vessels (Lyve-1) in fibrotic lungs of mice treated with bleomycin (Bleo), bleomycin + AG-1296 (Bleo + AG-1296) or in healthy control lungs of PBS-treated mice, respectively at day 28 on tissue of early, intermediate, and late stage fibrosis. Scale bars equal 100 μm. (B) Quantitative analysis of HA in lungs at day 28 after treatment with bleomycin, bleomycin + AG-1296 or PBS, respectively (controls n = 3, Bleo n = 6, Bleo + AG-1296 n = 6). (C) Immunodetection of fibroblasts (FSP) and lymphatic vessels (VEGFR3) in lungs of Bleo-, Bleo + AG-1296–, and PBS-treated mice, respectively, on tissue showing early, intermediate and late stage fibrosis at day 28. Scale bars equal 100 μm. (D) Quantitative analysis of FSP-positive cells at day 28 in Bleo, Bleo + AG-1296, and PBS-treated mice, respectively (controls n = 15, Bleo n = 29, Bleo + AG-1296 n = 13). Error bars show SEM.

Aberrant mural cell recruitment results in perilymphatic accumulation of hyaluronan with subsequent formation of fibrotic lesions. (A) Simultaneous immunodetection of HA and lymphatic vessels (Lyve-1) in fibrotic lungs of mice treated with bleomycin (Bleo), bleomycin + AG-1296 (Bleo + AG-1296) or in healthy control lungs of PBS-treated mice, respectively at day 28 on tissue of early, intermediate, and late stage fibrosis. Scale bars equal 100 μm. (B) Quantitative analysis of HA in lungs at day 28 after treatment with bleomycin, bleomycin + AG-1296 or PBS, respectively (controls n = 3, Bleo n = 6, Bleo + AG-1296 n = 6). (C) Immunodetection of fibroblasts (FSP) and lymphatic vessels (VEGFR3) in lungs of Bleo-, Bleo + AG-1296–, and PBS-treated mice, respectively, on tissue showing early, intermediate and late stage fibrosis at day 28. Scale bars equal 100 μm. (D) Quantitative analysis of FSP-positive cells at day 28 in Bleo, Bleo + AG-1296, and PBS-treated mice, respectively (controls n = 15, Bleo n = 29, Bleo + AG-1296 n = 13). Error bars show SEM.

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