ABSTRACT
TM6SF2, predominantly expressed in the liver and intestine, is closely associated with lipid metabolism. We have demonstrated the presence of TM6SF2 in VSMCs within human atherosclerotic plaques. Subsequent functional studies were conducted to investigate its role in lipid uptake and accumulation in human vascular smooth muscle cells (HAVSMCs) using siRNA knockdown and overexpression techniques. Our results showed that TM6SF2 reduced lipid accumulation in oxLDL-stimulated VSMCs, likely through the regulation of lectin-like oxLDL receptor 1 (LOX-1) and scavenger receptor cluster of differentiation 36 (CD36) expression. We concluded that TM6SF2 plays a role in HAVSMC lipid metabolism with opposing effects on cellular lipid droplet content by downregulation of LOX-1 and CD36 expression.
Subject(s)
Muscle, Smooth, Vascular , Scavenger Receptors, Class E , Humans , Muscle, Smooth, Vascular/metabolism , Scavenger Receptors, Class E/genetics , Lipoproteins, LDL/pharmacology , Lipoproteins, LDL/metabolism , Myocytes, Smooth Muscle/metabolism , Down-Regulation , Liver/metabolism , Membrane Proteins/metabolismABSTRACT
Objective: The individual cascades of the insulin-like growth factor-1 (IGF-1) signaling pathway and the molecular mechanism of aging have not been fully clarified. In the current study, we explored the effect of DNA polymerase delta 1 (POLD1) on the IGF-1 signaling pathway in cell aging. Methods: First, we analyzed the relationship between IGF-1 and POLD1 expression in aging. To investigate the effect of IGF-1 on POLD1 expression and aging, the 2BS cells were incubated with young-age or old-age human serum, IGF-1 protein, or linsitinib. Next, the effect of IGF-1 on aging was examined in the 2BS cells with increased or decreased POLD1 expression to clarify the molecular mechanism. Results: In this study, we found that IGF-1 expression increased and POLD1 expression decreased with aging in human serum and hippocampal tissues of SAMP8 mice, and a negative relationship between IGF-1 and POLD1 expression was observed. Furthermore, the cells cultured with old-age human serum or IGF-1 showed lower POLD1 expression and more pronounced senescence characteristics, and the effect could be reversed by treatment with linsitinib or overexpression of POLD1, while the effect of linsitinib on cell aging could be reversed with the knockdown of POLD1. Conclusion: Taken collectively, our findings demonstrate that IGF-1 promotes aging by binding to IGF-1R and inhibiting the expression of POLD1. These findings offer a new target for anti-aging strategies.
Subject(s)
Cellular Senescence , Insulin-Like Growth Factor I , Humans , Animals , Mice , Insulin-Like Growth Factor I/pharmacology , Aging , Hippocampus , DNA Polymerase IIISubject(s)
Alzheimer Disease/diagnosis , Membrane Glycoproteins/blood , Receptors, Immunologic/blood , Aged , Aged, 80 and over , Animals , Biomarkers/blood , Cognitive Dysfunction , Female , Humans , Male , Mental Status and Dementia Tests , Mice , Middle Aged , Models, Animal , Morris Water Maze Test , Parkinson Disease/diagnosis , ROC Curve , Sensitivity and SpecificityABSTRACT
A Gd27.5La27.5Al20Co20Fe5 bulk metallic glass (BMG) was synthesized by replacing 50% of the Gd element with the relatively cheap La element. The BMG has a rather high glass forming ability and the predicted critical diameter is about 7 mm by the differential scanning calorimetry (DSC) measurements. The BMG exhibits a medium range of refrigerant capacity (RC). The replacement of Gd with La leads to a slight reduction of the corresponding refrigerant efficiency of the alloy. However, the high value of magnetic entropy changes (-ΔS(m)peak) and low cost still indicates that the Gd27.5La27.5Al20Co20Fe5 BMG can be regarded as a good magnetic refrigerant candidate.
