Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Mol Biol Rep. 2013 Dec;40(12):6863-72. doi: 10.1007/s11033-013-2804-z. Epub 2013 Oct 5.
Recent researches indicate that PGRN is closely related to diabetes and is regarded as a novel adipokine associated with obesity development, affecting adipocyte biology. In the present study, we investigated the effects and mechanisms of PGRN on porcine preadipocytes differentiation. Porcine preadipocytes were induced to differentiation with the addition of lentivirius-expressed PGRN shRNA at the early or late stage of induction period, and in the presence or absence of recombinant PGRN protein. The effects of PGRN on adipogenic genes expression and ERK activation were investigated. At the early stage of induction, knockdown of PGRN promoted differentiation, evidenced by enhanced lipid accumulation, upregulation of adipocyte markers, as well as master adipogenic transcription factors, PPARγ and C/EBPα. While, decreasing PGRN expression at the late stage of induction (day 3) had no effect on differentiation. These results suggested that PGRN functions in the early adipogenic events. Conversely, porcine preadipocytes differentiation was impaired by MDI and recombinant PGRN protein induction, the expressions of adipocyte markers were decreased. Further studies revealed that PGRN can specifically facilitate ERK1,2 activation, and this activation can be abolished by U0126. Moreover, PPARγ phosphorylation at serine 112 site was increased by PGRN treatment, which could reduce the transcriptional activity of PPARγ. We conclude that PGRN inhibits adipogenesis in porcine preadipocytes partially through ERK activation mediated PPARγ phosphorylation.
最近的研究表明，PGRN 与糖尿病密切相关，被认为是一种与肥胖发展相关的新型脂肪因子，影响脂肪细胞生物学。在本研究中，我们研究了 PGRN 对猪前体脂肪细胞分化的影响及其机制。在诱导期的早期或晚期，通过添加慢病毒表达的 PGRN shRNA，以及重组 PGRN 蛋白，诱导猪前体脂肪细胞分化。研究了 PGRN 对脂肪生成基因表达和 ERK 激活的影响。在诱导的早期阶段，PGRN 的敲低促进了分化，表现为脂滴积累增加、脂肪细胞标志物上调以及主脂肪生成转录因子 PPARγ 和 C/EBPα 的上调。然而，在诱导的晚期（第 3 天）降低 PGRN 表达对分化没有影响。这些结果表明 PGRN 在早期脂肪生成事件中发挥作用。相反，猪前体脂肪细胞分化被 MDI 和重组 PGRN 蛋白诱导所抑制，脂肪细胞标志物的表达减少。进一步的研究表明，PGRN 可以特异性地促进 ERK1、2 的激活，而这种激活可以被 U0126 所阻断。此外，PGRN 处理后 PPARγ 在丝氨酸 112 位的磷酸化增加，从而降低了 PPARγ 的转录活性。我们得出结论，PGRN 通过 ERK 激活介导的 PPARγ 磷酸化，部分抑制猪前体脂肪细胞的脂肪生成。
