Mouse Anti-Mouse Fibroblast Activation Protein monoclonal antibody, clone 84.4

Fluoride has been considered as a risk factor of cardiovascular disease due to its endothelial toxicology. However, the mechanism underlying the endothelial toxicity of fluoride has not been clearly illustrated. MiR-200c-3p was strongly linked with endothelial function and its level is increased in serum of fluorosis patients, but it is unclear the role of miR-200c-3p in the fluoride induced endothelial dysfunction. In this study, we confirmed that fluoride exposure induced the apoptosis of endothelial cells both in established rats model and cultured human umbilical vein endothelial cells (HUVECs). And miR-200c-3p was found to be upregulated in NaF treated HUVECs. Fluoride stimulation increased caspase-dependent apoptosis through miR-200c-3p upregulation, with repressing expression of its target gene Fas-associated phosphatase 1 (Fap-1), which functioned as Fas inhibitor. This resulted in activation of Fas-associated extrinsic apoptosis via interaction with increased Fas, Fadd, Cleaved Caspase-8 and Cleaved Caspase-3. The activation of Fas-associated extrinsic apoptosis was abrogated by miR-200c-3p inhibitor. Furthermore, the antiapoptotic effect of downregulated miR-200c-3p was restored by Fap-1 siRNA. These results suggested a determinant role of the miR-200c-3p/Fap-1 axis in fluoride induced endothelial apoptosis. (C) 2020 Elsevier Ltd. All rights reserved.

The Fibroblast Growth Factor 21 (FGF21) is considered an attractive therapeutic target for obesity and obesity-related disorders due to its beneficial effects in lipid and carbohydrate metabolism. FGF21 response is essential under stressful conditions and its metabolic effects depend on the inducer factor or stress condition. FGF21 seems to be the key signal which communicates and coordinates the metabolic response to reverse different nutritional stresses and restores the metabolic homeostasis. This review is focused on describing individually the FGF21-dependent metabolic response activated by some of the most common nutritional challenges, the signal pathways triggering this response, and the impact of this response on global homeostasis. We consider that this is essential knowledge to identify the potential role of FGF21 in the onset and progression of some of the most prevalent metabolic pathologies and to understand the potential of FGF21 as a target for these diseases. After this review, we conclude that more research is needed to understand the mechanisms underlying the role of FGF21 in macronutrient preference and food intake behavior, but also in beta-klotho regulation and the activity of the fibroblast activation protein (FAP) to uncover its therapeutic potential as a way to increase the FGF21 signaling.