Fig 7.
TGF-β1 induces LOXL4 expression by ERK-mediated phosphorylation of Fra2. (A) Effects of MAPK inhibitors SB203580 (p38, 10 μM), CI-1040 (ERK, 2 μM), and SP600125 (JNK, 25 μM) on luciferase activity of LOXL4 promoter luciferase construct. Values are represented as normalized luciferase units (mean ± SEM; n = 3). *, P < 0.05 versus vehicle (dimethyl sulfoxide [DMSO] for SB203580 and CI-1040 and ethanol for SP600125) upon TGF-β1 stimulation. (B and C) Dose dependence analysis of the effect of the ERK inhibitor CI-1040 on TGF-β1-induced LOXL4 promoter activity (B) and mRNA expression (C). (D) Time course of the effect of TGF-β1 on ERK activation (phospho-ERK [p-ERK]) and Fra2 phosphorylation (p-Fra2) analyzed by Western blotting in extracts from cells treated with vehicle (control) or with CI-1040 (2 μM). Values above the blots refer to the p-Fra2/β-actin and p-ERK/total ERK ratios after densitometric analysis. Results are representative of three experiments.