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. 2018 Jun 1;197(11):1443–1456. doi: 10.1164/rccm.201707-1519OC

Figure 7.

Figure 7.

Figure 7.

Role of Gas6/TAM (Tyro3, Axl, and Mertk) receptor activation in experimental pulmonary fibrosis. Treatment protocol is as follows: humanized SCID/Bg mice were injected with idiopathic pulmonary fibrosis fibroblasts and subsequently treated orally with R428 (5 mg/kg), BIBF1120 (30 mg/kg), or the appropriate vehicle. (A) Treatments were given from Day 0 to Day 35 after fibroblast injection, and lungs were analyzed at Day 35. (B) Gas6 and Axl gene expression in lungs of other groups of SCID/Bg mice that received either idiopathic pulmonary fibrosis or normal fibroblasts by intravenous injection and unchallenged mice (naive), and transcripts were evaluated at Days 7, 21, and 35 after injection. (C–F) The following analyses at Day 35 after treatments in humanized SCID/Bg mice are shown: hydroxyproline levels (C), p-Axl quantification (D), transcript expression of murine PDGFRα, PDGFRβ, Col1a2, FN1 (E), and transcript expression of Gas6, Axl, Mertk, and Tyro3 (F). (G) Representative images of Masson trichrome staining in whole lungs and affected areas (see insets). Whole-lung p-Axl was determined using a PathScan phospho-Axl (panTyr) sandwich ELISA kit. Data are mean ± SEM, n = 3–5 per group. *P ≤ 0.05; **P ≤ 0.01. **P is compared with the vehicle group. Axl = anexelekto; BIBF = BIBF1120 (nintedanib); col1a2 = collagen 1 α 2; D = day; fn1 = fibronectin 1; Gas6 = growth arrest–specific 6; IPF = idiopathic pulmonary fibrosis; Mertk = MER proto-oncogene, tyrosine kinase; Mu = Mus musculus; p-Axl = phosphorylated Axl; p.o. = per os (oral gavage); pdgfr = platelet-derived growth factor receptor; Tyro3 = TYRO3 protein tyrosine kinase 3.