Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
J Biotechnol. 2024 Nov 20;395:95-99. doi: 10.1016/j.jbiotec.2024.09.016. Epub 2024 Sep 26.
Adiponectin (ADPN) exerts various cellular and metabolic functions by activating signaling pathways, including extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathways, the protein kinase B (Akt) pathway, and the p38 mitogen-activated protein kinase (MAPK) pathway. However, generating functional recombinant human adiponectin (hADPN) in bacterial or mammalian cells is challenging. Although ADPN agonist peptides have been developed, problems like stability, solubility, and affinity for receptors remain. Recently, a genome-edited chicken bioreactor system was established, ensuring efficient ADPN production with optimal post-transcriptional modifications. We assessed the ability of egg white (EW)-derived hADPN, commercial hADPN, various ADPN agonist peptides, and globular ADPN on activation of the ERK1/2, Akt, and p38 MAPK pathways. EW-derived hADPN, abundant in hexamers and high molecular weight multimers, significantly phosphorylated ERK1/2 in serum-starved HEK293 cells after 15 min of treatment. Comparative analysis revealed that EW-derived hADPN and commercial hADPN induced greater phosphorylation of ERK1/2, Akt, and p38 MAPK than ADPN agonist peptides and globular ADPN, with EW-derived hADPN showing the highest activation. In summary, the finding that EW-derived hADPN strongly activates the ERK1/2, Akt, p38 MAPK signaling pathways highlights that an ADPN production system based on genome-edited chickens is an advantageous alternative to existing methods.
脂联素（ADPN）通过激活信号通路，包括细胞外信号调节蛋白激酶 1 和 2（ERK1/2）通路、蛋白激酶 B（Akt）通路和 p38 丝裂原激活蛋白激酶（MAPK）通路，发挥各种细胞和代谢功能。然而，在细菌或哺乳动物细胞中生成功能性重组人脂联素（hADPN）具有挑战性。尽管已经开发出 ADPN 激动肽，但仍然存在稳定性、溶解度和受体亲和力等问题。最近，建立了一种经过基因组编辑的鸡生物反应器系统，可确保高效生产 hADPN，并进行最佳的转录后修饰。我们评估了蛋清（EW）衍生的 hADPN、商业 hADPN、各种 ADPN 激动肽和球形 ADPN 激活 ERK1/2、Akt 和 p38 MAPK 通路的能力。在血清饥饿的 HEK293 细胞中，经过 15 分钟处理后，富含六聚体和高分子量多聚体的 EW 衍生的 hADPN 显著磷酸化 ERK1/2。比较分析表明，EW 衍生的 hADPN 和商业 hADPN 诱导 ERK1/2、Akt 和 p38 MAPK 的磷酸化程度高于 ADPN 激动肽和球形 ADPN，而 EW 衍生的 hADPN 表现出最高的激活作用。总之，EW 衍生的 hADPN 强烈激活 ERK1/2、Akt、p38 MAPK 信号通路的发现表明，基于基因组编辑鸡的 ADPN 生产系统是现有方法的有利替代方案。
