Attenuation of the LPS-induced, ERK-mediated upregulation of fibrosis-related factors FGF-2, uPA, MMP-2, and MMP-9 by Carthamus tinctorius L in cardiomyoblasts.
Environ Toxicol. 2017 Mar ;32(3):754-763. Epub 2016 Apr 20. PMID: 27098997
Severe and potentially fatal hypotension and cardiac contractile dysfunction are common symptoms in patients with sepsis. LPS was previously found to dramatically upregulate expression of fibrosis-related factors FGF-2, uPA, MMP-2, and MMP-9 in primary cardiac fibroblasts. MMPs are capable of denaturing and degrading fibrillar collagens and other components of the extracellular matrix (ECM). Studies have shown that dysregulation of expression of MMPs is associated with development of myocardial extracellular matrix remodeling and cardiac fibrosis, which contribute to progression of heart failure. In this study, H9c2 cells and cardiac fibroblasts were divided into five treatment groups: control, LPS (1μg/mL) and three concentrations of FC(Carthami Flos ethanolic extract) (31.25, 62.5, and 125μg/mL). Phosphorylation of ERK-1/2 was observed to be rapidly induced upon treatment with LPS. In contrast, it was significantly suppressed by the administration of FC(125μg/mL). Effects of FCon LPS-induced MMP-2 and MMP-9 expression in H9c2 cells occurred directly through ERK1/2 were determined. H9c2 cells were therefore pretreated with EGF-R to activate ERK pathway. Both protein levels of MMP-2 and MMP-9 and immunefluorescent signals of MMP-9 were significantly enhanced by EGFR. In contrast, MMP-2 and MMP-9 were significantly reduced after FCadministration. Based on these findings, the authors concluded that FCelicits a protective effect against LPS-induced cardio-fibrosis through the ERK1/2 pathway. Carthamus tinctorius L may potentially serve as a cardio-protective agent against LPS- induced cardiac fibrosis.© 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 754-763, 2017.