Braun Platon, Alawi Malik, Saygi Ceren, Pantel Klaus, Wagers Amy J
Harvard University, Department of Stem Cell and Regenerative Biology, Cambridge, MA, United States.
University Medical Center Hamburg-Eppendorf, Department of Tumor Biology, Hamburg, Germany.
Genet Mol Biol. 2024 Jul 15;47(2):e20230304. doi: 10.1590/1678-4685-GMB-2023-0304. eCollection 2024.
Growth differentiation factor 11 (GDF11) and myostatin (MSTN/GDF8) are closely related members of the transforming growth factor β (TGFβ) superfamily, sharing structural homology. Despite these structural similarities, recent research has shed light on the distinct roles these ligands play within muscle tissue. This study aims to uncover both the differences and similarities in gene expression at the transcriptome level by utilizing RNA sequencing. We conducted experiments involving five distinct groups, each with three biological replicates, using C2C12 cell cultures. The cells were subjected to high-throughput profiling to investigate disparities in gene expression patterns following preconditioning with either GDF11 or MSTN at concentrations of 1 nM and 10 nM, respectively. In addition, control groups were established. Our research revealed concentration-dependent gene expression patterns, with 38 genes showing significant differences when compared to the control groups. Notably, GADD45, SMAD7, EGR-1, and HOXA3 exhibited significant differential expression. We also conducted an over-representation analysis, highlighting the activation of MAPK and JNK signaling pathways, along with GO-terms related to genes that negatively regulate metabolic processes, biosynthesis, and protein phosphorylation. This study unveiled the activation of several genes not previously discussed in existing literature whose full biological implications are yet to be determined in future research.
生长分化因子11（GDF11）和肌肉生长抑制素（MSTN/GDF8）是转化生长因子β（TGFβ）超家族中密切相关的成员，具有结构同源性。尽管存在这些结构上的相似性，但最近的研究揭示了这些配体在肌肉组织中所起的不同作用。本研究旨在通过RNA测序揭示转录组水平上基因表达的差异和相似性。我们使用C2C12细胞培养物进行了涉及五个不同组的实验，每组有三个生物学重复。细胞经过高通量分析，以研究分别用1 nM和10 nM浓度的GDF11或MSTN预处理后基因表达模式的差异。此外，还设立了对照组。我们的研究揭示了浓度依赖性基因表达模式，与对照组相比，有38个基因表现出显著差异。值得注意的是，生长停滞和DNA损伤诱导蛋白45（GADD45）、SMAD家族成员7（SMAD7）、早期生长反应蛋白1（EGR-1）和同源框A3（HOXA3）表现出显著的差异表达。我们还进行了过表达分析，突出了丝裂原活化蛋白激酶（MAPK）和应激活化蛋白激酶（JNK）信号通路的激活，以及与负调控代谢过程、生物合成和蛋白质磷酸化的基因相关的基因本体（GO）术语。本研究揭示了一些现有文献中未讨论过的基因的激活，其完整的生物学意义有待未来研究确定。
