Fig 2: Osteogenic differentiation of human MSC seeded on decellularized matrices from fibroblasts exposed to LOX/BMP1 supernatants. The capacity of human MSC to differentiate into osteoblasts in substrates without matrix, with matrix from TGF-ß-stimulated fibroblasts exposed to control medium or with LOX/BMP1 was assessed by microscopic examination (A) and quantified by spectrophotometry (B) using Alizarin Red S staining. Micrographs shown correspond to representative results of staining performed twice with two independent preparations. Values are represented as absorbance at 405 nm (mean ± SEM, n = 6; *P < 0.05 vs no matrix, and #P < 0.05 vs matrix fibroblast-derived matrix under control medium). Bars = 50 µm.

Fig 3: LOX reduced the degree of PQ-induced epithelial-to-mesenchymal transition and had no effect on HIF-1a expression. (A) The level of LOX mRNA in both LOX-silenced cell lines was detected by RT-qPCR. (B) Levels of LOX, E-cadherin, a-SMA and GAPDH proteins were detected by western blotting. GAPDH served as a loading control. (C) Morphological changes were detected using a phase-contrast microscope. Scale bars, 100 µm. (D) The level of HIF-1a mRNA in both LOX-silenced cell lines was detected by RT-qPCR. (E) Levels of HIF-1a and GAPDH proteins were detected by western blotting. $P<0.05 vs. control; *P<0.05 vs. sicontrol; #P<0.05 vs. sicontrol + PQ. LOX, lysyl oxidase; PQ, paraquat; HIF-1a, hypoxia-inducible factor-1a; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; a-SMA, a-smooth muscle actin; DMSO, dimethyl sulfoxide.

Fig 4: Inhibition of HIF-1a and LOX decreases ß-catenin expression in vitro. Levels of ß-catenin mRNA in (A) HIF-1a- and (B) LOX-silenced A549 and RLE-6TN cells were detected using reverse transcription-quantitative polymerase chain reaction. The expression of ß-catenin protein in (C) HIF-1a- and (D) LOX-silenced cells was detected using western blotting. GAPDH served as a loading control. $P<0.05 vs. control; *P<0.05 vs. sicontrol; #P<0.05 vs. sicontrol + PQ. HIF-1a, hypoxia-inducible factor-1a; LOX, lysyl oxidase; DMSO, dimethyl sulfoxide; PQ, paraquat.

Fig 5: Associations of cardiovascular magnetic resonance parameters with collagen metabolism.(A, B) Correlations between myocardial LOX expression and insoluble collagen fraction and total collagen. (C, D) Correlations between PFR and insoluble collagen fraction and myocardial LOX expression. (E, F) Correlations between PER-E and insoluble collagen fraction and myocardial LOX expression. A.D.U., arbitrary densitometric units; HOCM, hypertrophic obstructive cardiomyopathy; LOX, lysyl oxidase; PER-E, early peak emptying rate; and PFR, peak filling rate.