In cardiac fibroblasts, interferon-beta attenuates differentiation, collagen synthesis, and TGF-β1-induced collagen gel contraction

•IFN-β through STAT1 and STAT2 activation reduces α-SMA levels in cardiac fibroblasts exposed to TGF-β1.•IFN-β via STAT1 phosphorylation decreases TGF-β1-induced pro-collagen I protein and collagen gel contraction.•IFN-β through STAT1 and STAT2 activation blocks fetal bovine serum-induced cardiac fibroblast migration. Cardiac fibroblasts (CF) play a key role in the homeostasis of the extracellular matrix in cardiac tissue and are newly recognized as inflammatory supporter cells. Besides, CF-to-Cardiac myofibroblast differentiation is commanded by TGF-b, through SMAD signaling pathways, and these last cells are strongly implicated in cardiac fibrosis. In the heart IFN-β is produced by CF; however, the role of IFN-β, STAT proteins, and STAT-homo or heterodimers in the regulation of CF function with or without a fibrotic environment is unknown. CF were isolated from hearts of adult rats, and by western blot analysis we studied STAT1, STAT2, and STAT3 phosphorylation and through specific siRNA against these proteins we analyzed their role in CF functions such as differentiation (α-SMA expression); and pro-collagen type-I synthesis and secretion expression levels; collagen gels contraction and CF migration. In cultured adult rats CF, IFN-β increases phosphorylation of STAT1, STAT2, and STAT3. Both STAT1 and STAT2 were involved in decreasing α-SMA and CF migration induced by TGF-β1. Also, IFN-β through STAT1 regulated pro-collagen type-I protein expression levels, and collagen gels contraction induced by TGF-β1. STAT3 was not involved in any effects of IFN-β studied. In conclusion, IFN-β through STAT1 and STAT2 shows antifibrotic effects on CF TGF-β1-treated, whereas STAT3 did not participate in such effect.