Chang Ying-Hua, Ye Lei, Cai Wenxuan, Lee Yoonkyu, Guner Huseyin, Lee Youngsook, Kamp Timothy J, Zhang Jianyi, Ge Ying
Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA.
Human Proteomics Program, University of Wisconsin-Madison, Madison, WI, USA.
Proteomics. 2015 Aug;15(15):2560-7. doi: 10.1002/pmic.201500131.
Intramyocardial transplantation of cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) derived from human induced pluripotent stem cells (hiPSCs) has beneficial effects on the post-infarction heart. However, the mechanisms underlying the functional improvements remain undefined. We employed large-scale label-free quantitative proteomics to identify proteins that were differentially regulated following cellular transplantation in a swine model of myocardial infarction (MI). We identified 22 proteins that were significantly up-regulated after trilineage cell transplantation compared to both MI and Sham groups. Among them, 12 proteins, including adenylyl cyclase-associated protein 1 and tropomodulin-1, are associated with positive regulation of muscular contraction whereas 11 proteins, such as desmoplakin and zyxin, are involved in embryonic and muscular development and regeneration. Moreover, we identified 21 proteins up-regulated and another 21 down-regulated in MI, but reversed after trilineage cell transplantation. Proteins up-regulated after MI but reversed by transplantation are related to fibrosis and apoptosis. Conversely, proteins down-regulated in MI but restored after cell therapy are regulators of protein nitrosylation. Our results show that the functionally beneficial effects of trilineage cell therapy are accompanied by differential regulation of protein expression in the recipient myocardium, which may contribute to the improved cardiac function.
将源自人诱导多能干细胞（hiPSC）的心肌细胞（CM）、内皮细胞（EC）和平滑肌细胞（SMC）进行心肌内移植，对心肌梗死后的心脏具有有益作用。然而，功能改善背后的机制仍不明确。我们采用大规模无标记定量蛋白质组学方法，以鉴定在猪心肌梗死（MI）模型中细胞移植后差异调节的蛋白质。我们鉴定出22种蛋白质，与MI组和假手术组相比，三系细胞移植后这些蛋白质显著上调。其中，12种蛋白质，包括腺苷酸环化酶相关蛋白1和原肌球蛋白1，与肌肉收缩的正调控相关，而11种蛋白质，如桥粒斑蛋白和斑联蛋白，参与胚胎和肌肉发育及再生。此外，我们鉴定出21种在MI中上调而在三系细胞移植后逆转的蛋白质，以及另外21种在MI中下调而在细胞治疗后恢复的蛋白质。MI后上调但移植后逆转的蛋白质与纤维化和细胞凋亡相关。相反，MI中下调但细胞治疗后恢复的蛋白质是蛋白质亚硝基化的调节因子。我们的结果表明，三系细胞治疗的功能有益作用伴随着受体心肌中蛋白质表达的差异调节，这可能有助于改善心脏功能。
