Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul, 120-752, Korea.
Department of Integrated OMICS for Biomedical Sciences, Graduate School, Yonsei University, Seoul, 120-749, Korea.
Sci Rep. 2017 Nov 1;7(1):14833. doi: 10.1038/s41598-017-12512-2.
Mesenchymal stem cells have the capacity to give rise to multiple cell types, such as adipocytes, osteoblasts, chondrocytes, and myocytes. However, the molecular events responsible for the lineage specification and differentiation of mesenchymal stem cells remain unclear. Using gene expression profile studies, we determined that Scavenger receptor class A, member 5 (SCARA5) is a novel mediator of adipocyte commitment. SCARA5 was expressed at a higher level in committed A33 preadipocyte cells compared to C3H10T1/2 pluripotent stem cells. Gain- and loss-of-function studies likewise revealed that SCARA5 acts as a mediator of adipocyte commitment and differentiation in both A33 and C3H10T1/2 cells. RNAi-mediated knockdown of SCARA5 in A33 cells markedly inhibited the adipogenic potential, whereas overexpression of SCARA5 enhanced adipocyte differentiation in C3H10T1/2 cells. We also demonstrated that the focal adhesion kinase (FAK) and ERK signaling pathways is associated with the SCARA5-mediated response, thereby modulating adipocyte lineage commitment and adipocyte differentiation. Additionally, glucocorticoids induced the expression of SCARA5 in differentiating adipocytes through glucocorticoids response elements (GRE) in the SCARA5 promoter. Taken together, our study demonstrates that SCARA5 is a positive regulator in adipocyte lineage commitment and early adipogenesis in mesenchymal stem cells.
间充质干细胞具有分化为多种细胞类型的能力，如脂肪细胞、成骨细胞、软骨细胞和肌细胞。然而，导致间充质干细胞谱系特化和分化的分子事件仍不清楚。通过基因表达谱研究，我们确定了清道夫受体家族 A 成员 5（SCARA5）是脂肪细胞定向的新型介质。与多能干细胞 C3H10T1/2 相比，SCARA5 在定向的 A33 前脂肪细胞中表达水平更高。增益和缺失功能研究同样表明，SCARA5 在 A33 和 C3H10T1/2 细胞中作为脂肪细胞定向和分化的介质起作用。RNAi 介导的 SCARA5 在 A33 细胞中的敲低显著抑制了脂肪生成潜能，而 SCARA5 的过表达增强了 C3H10T1/2 细胞中的脂肪细胞分化。我们还证明了粘着斑激酶（FAK）和 ERK 信号通路与 SCARA5 介导的反应相关，从而调节脂肪细胞谱系定向和脂肪细胞分化。此外，糖皮质激素通过 SCARA5 启动子中的糖皮质激素反应元件（GRE）诱导分化脂肪细胞中 SCARA5 的表达。总之，我们的研究表明，SCARA5 是间充质干细胞中脂肪细胞谱系定向和早期脂肪生成的正向调节剂。
