Key Laboratory of System Bio-medicine of Jiangxi Province, Jiujiang University, Jiujiang, 332000, China.
Key Laboratory of System Bio-medicine of Jiangxi Province, Jiujiang University, Jiujiang, 332000, China.
Biochem Biophys Res Commun. 2020 Mar 26;524(1):163-168. doi: 10.1016/j.bbrc.2020.01.060. Epub 2020 Jan 23.
Stanniocalcin-2 (STC2) is a glycoprotein that has been found to play key roles in the regulation of cancer, diabetes mellitus, and osteogenesis. Herein we sought to extend these past studies by examining the importance of STC2 in the context of human mesenchymal stem cell (hMSC) adipogenic differentiation and exploring the mechanisms underlying such importance. We found that STC2 expression was significantly reduced on day 7 of hMSC adipogenesis. When we deliberately overexpressed STC2 in these cells, this resulted in significantly decreased expression of both peroxisome proliferator-activated receptor γ (PPARγ) and Fatty Acid Binding Protein-4 (FABP4) together with increased extracellular-signal regulated kinase 1/2 (ERK1/2) phosphorylation and markedly reduced lipid droplet formation within cells. Treatment of cells using the ERK inhibitor U0126 disrupted this ERK1/2 phosphorylation and restored the adipogenic differentiation of these hMSCs. When we instead knocked down STC2 expression, the opposite phenotypes were observed. Together these findings thus reveal that STC2 modulates ERK1/2 signaling in hMSCs so as to suppress their adipogenic differentiation.
钙网蛋白 2（STC2）是一种糖蛋白，已被发现在癌症、糖尿病和成骨作用的调节中发挥关键作用。在此，我们试图通过研究 STC2 在人骨髓间充质干细胞（hMSC）成脂分化中的重要性，并探索其重要性的潜在机制，来扩展这些过去的研究。我们发现 hMSC 成脂分化第 7 天 STC2 的表达明显降低。当我们故意在这些细胞中过表达 STC2 时，这导致过氧化物酶体增殖物激活受体 γ（PPARγ）和脂肪酸结合蛋白 4（FABP4）的表达显著降低，同时细胞外信号调节激酶 1/2（ERK1/2）磷酸化增加，细胞内脂滴形成明显减少。使用 ERK 抑制剂 U0126 处理细胞会破坏这种 ERK1/2 磷酸化，并恢复这些 hMSC 的成脂分化。而当我们敲低 STC2 的表达时，则观察到相反的表型。这些发现共同揭示，STC2 通过调节 hMSC 中的 ERK1/2 信号来抑制其成脂分化。
