Goudarzi Farjam, Mohammadalipour Adel, Khodadadi Iraj, Karimi Sheno, Mostoli Rezvan, Bahabadi Majid, Goodarzi Mohammad Taghi
Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Clinical Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Mol Biotechnol. 2018 Apr;60(4):279-289. doi: 10.1007/s12033-018-0071-x.
Differentiation process of mesenchymal stem cells (MSCs) into adipocyte is involved in obesity. Multiple factors such as Ca play important roles in different stages of this process. Because of the complicated roles of Ca in adipogenesis, the aim of present investigation was to study the influx and efflux of Ca into and out of the cells during adipogenesis. Adipose-derived MSCs were used to differentiate into adipocytes. MSCs were exposed to 2.5 mM Ca or 1.8 mM Ca plus calcium ionophore, A23187, for 3 days. Lipid staining, triglycerides (TG) content, and glyceraldehyde phosphate dehydrogenase (GAPDH) activity were evaluated to confirm the efficiency of the differentiation. Gene expression of GLUT4, PPARγ2, RAR-α, and calreticulin, as well as the protein levels of GLUT4 and PPARγ2 were determined. Ca and in particular Ca plus A23187 significantly lowered the efficiency of differentiation accompanied by decrease in intracellular TG deposits, GAPDH activity and alleviation of gene, and protein levels of GLUT4 and PPARγ2. While calreticulin and RAR-α were remarkably upregulated in A23187 group. This study showed the inhibitory effects of calcium in adipogenesis. Additionally, it indicated the greater inhibitory effect of calreticulin and RAR-α in controlling adipogenesis by higher levels of calcium.
间充质干细胞（MSCs）向脂肪细胞的分化过程与肥胖有关。钙等多种因素在这一过程的不同阶段发挥着重要作用。由于钙在脂肪生成中的作用复杂，本研究的目的是研究脂肪生成过程中钙进出细胞的内流和外流情况。采用脂肪来源的间充质干细胞分化为脂肪细胞。将间充质干细胞暴露于2.5 mM钙或1.8 mM钙加钙离子载体A23187中3天。通过脂质染色、甘油三酯（TG）含量和甘油醛-3-磷酸脱氢酶（GAPDH）活性评估来确认分化效率。测定葡萄糖转运蛋白4（GLUT4）、过氧化物酶体增殖物激活受体γ2（PPARγ2）、视黄酸受体α（RAR-α）和钙网蛋白的基因表达，以及GLUT4和PPARγ2的蛋白水平。钙尤其是钙加A23187显著降低了分化效率，同时细胞内TG沉积、GAPDH活性降低，GLUT4和PPARγ2的基因及蛋白水平也有所减轻。而钙网蛋白和RAR-α在A23187组中显著上调。本研究显示了钙对脂肪生成的抑制作用。此外，它还表明钙网蛋白和RAR-α在通过更高水平的钙控制脂肪生成方面具有更大的抑制作用。
