To investigate the inhibitory effect of endostatin on pulmonary fibrosis in mice via the Notch1/platelet-derived growth factor (PDGF) signaling pathway.

A total of 30 mice were randomly divided into a control group, a model group and an endostatin group, with 10 mice in each group. Mice in the model and endostatin groups were given bleomycin (5 mg/kg) by intratracheal injection to establish a model of pulmonary fibrosis, and mice in the control group were injected with equal volume of isotonic NaCl solution. Then, mice in the endostatin group were given endostatin (2.3 mg/kg) daily, and mice in the control and model groups were injected with equal volume of isotonic NaCl solution, all by intraperitoneal injection for 21 days; afterwards, all mice were sacrificed. The left lung tissue was taken for pathological staining, and the right lung tissue was used to detect expression levels of Collagen I, Notch1/PDGF signaling pathway-related proteins [transforming growth factor-beta 1 (TGF-β1), Hes1, Hey1, PDGF-B, PDGF receptor-beta (PDGFR-β)], and pericyte proteins [Desmin, neuron-glial antigen 2 (NG2), alpha-smooth muscle actin (α-SMA)] by Western-blotting.

Under light microscope, the alveolar structure was intact and no abnormal collagen was found in the control group; the alveolar structure was destroyed and massive collagen was deposited in the model group; the alveolar structure was relatively intact and collagen significantly reduced in the endostatin group. The expression levels of Collagen I, TGF-β1, Hes1, Hey1, PDGF-B, PDGFR-β, Desmin, NG2 and α-SMA were significantly different among three groups (F = 12.068, 30.603, 29.757, 35.451, 16.059, 16.420, 24.512, 19.084, 28.102; all P < 0.001). Meanwhile, compared with the model group, the expression levels of Collagen I, TGF-β1, Hes1, Hey1, PDGF-B, PDGFR-β and α-SMA were much lower and the expression levels of Desmin and NG2 were much higher in the endostatin group (all P < 0.05). However, the expression levels of Collagen I, TGF-β1, Hes1, Hey1, PDGF-B, PDGFR-β, Desmin, NG2 and α-SMA showed no significant differences between the endostatin group and control group (all P>0.05).

Endostatin inhibits the transformation of pericytes into myofibroblasts by the Notch1/PDGF signaling pathway, and thereby restrains pulmonary fibrosis in mice.