Methionine sulfoxide reductase B1 (MsrB1), a member of the selenoprotein family and contributes significantly to the reduction of methionine sulfoxides produced from reactive oxygen species (ROS). However, few studies have examined the role of MsrB1 in tumors. Here We tested the proliferation and invasion in MsrB1 knockdown u2os cells under H2O2/thioredoxin. As shown in our result, knockdown of MsrB1 inhibited the proliferation of u2os cells and regulates mitogen-activated protein kinase (MAPK) pathway by down-regulation of Erk, MeK phosphorylation and p53 expression in u2os cells. In a xenograft tumorigenicity mice, MsrB1 knockdown effectively inhibited tumor growth. Furthermore, MsrB1 knockdown resulted in migration and invasion reducement of u2os cells. MsrB1 regulates epithelial-mesenchymal transition (EMT) via affecting cytoskeleton by increasing E-cadherin expression and decreasing N-cadherin, TGF-β1, slug, fibronectin, vimentin, c-myc, snail and β-catenin expressions. In vivo, MsrB1 shRNAi can inhibit lung metastasis in metastasis model. In conclusion, MsrB1 regulates proliferation and invasion of u2os cells by affecting MAPK pathway and EMT, and MsrB1 gene may be a novel therapeutic target against tumors.

FGF21, a special member of FGF superfamily, has been proven to have pleiotropic metabolic effects and many potential therapeutic action in various metabolic disorders. Vascular calcification (VC), a perplexing clinical issue, is a major risk factor for many cardiovascular diseases, especially for patients with some metabolic diseases. However, the role of FGF21 on VC in vivo remains unclear. Thus, in this study, we observed the effect and mechanism of FGF21 on VC induced by vitamin D3 plus nicotine (VDN) treated rats. After four weeks' treatment, the calcium overload is mainly manifested in the increased blood pressure, aortic calcium content and ALP activity. Also, the HE and Alizarin-red S staining showed the structural damage of calcified vessel walls. In addition, the level of endogenous FGF21/β-Klotho/FGFR1 axis was up-regulated in the aortas of VC rats. Furthermore, exogenous FGF21 treatment significantly ameliorated the aortic injury and calcification in VC rats, and the level of β-Klotho and FGFR1 were furtherly increase. Moreover, FGF21 inhibited the osteogenic transition of VSMCs by down-regulating the expression of bone-associated proteins such as osteopontin (OPN), osteocalcin (OCN) and bone morphogenetic protein-2 (BMP-2), together with restored the expression of SM22α and SM α-actin, which are two of lineage markers in VSMCs. We provide the first evidence that FGF21 can inhibit the development of VC by inhibiting the osteogenic transition of VSMCs in rats. FGF21 might be an efficient endogenous vasoprotective factor for calcification.