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生长分化因子11的生物信息学网络分析

Bioinformatics network analyses of growth differentiation factor 11.

作者信息

Zhang Feng, Yang Xia, Bao Zhijun

机构信息

Huadong Hospital Affiliated to Fudan University, 221 West Yan'an Road, Shanghai, 200040, China.

National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, 12 Mid Urumqi Road, Shanghai, 200040, China.

出版信息

Open Life Sci. 2022 Apr 26;17(1):426-437. doi: 10.1515/biol-2022-0044. eCollection 2022.

Abstract

Growth differentiation factor 11 (GDF11) has been implicated in rejuvenating functions in age-related diseases. The molecular mechanisms connecting GDF11 with these anti-aging phenomena, including reverse age-related cardiac hypertrophy and vascular and neurogenic rejuvenation, remain unclear. In this study, we sought to uncover the molecular functions of GDF11 using bioinformatics and network-driven analyses at the human gene and transcription levels using the gene co-expression network analysis, the protein-protein interaction network analysis, and the transcription factor network analysis. Our findings suggested that GDF11 is involved in a variety of functions, such as apoptosis, DNA repair, telomere maintenance, and interaction with key transcription factors, such as MYC proto-oncogene, specificity protein 1, and ETS proto-oncogene 2. The human skin fibroblast premature senescence model was established by UVB. The treatment with 10 ng/mL GDF11 in this cell model could reduce cell damage, reduce the apoptosis rate and the expression of caspase-3, and increase the length of telomeres. Therefore, our findings shed light on the functions of GDF11 and provide insights into the roles of GDF11 in aging.

摘要

生长分化因子11(GDF11)与年龄相关疾病中的功能恢复有关。GDF11与这些抗衰老现象(包括逆转与年龄相关的心脏肥大以及血管和神经再生)之间的分子机制仍不清楚。在本研究中,我们试图通过基因共表达网络分析、蛋白质-蛋白质相互作用网络分析和转录因子网络分析,在人类基因和转录水平上利用生物信息学和网络驱动分析来揭示GDF11的分子功能。我们的研究结果表明,GDF11参与多种功能,如细胞凋亡、DNA修复、端粒维持以及与关键转录因子(如MYC原癌基因、特异性蛋白1和ETS原癌基因2)的相互作用。通过紫外线B建立了人类皮肤成纤维细胞早衰模型。在该细胞模型中用10 ng/mL GDF11处理可减少细胞损伤,降低细胞凋亡率和半胱天冬酶-3的表达,并增加端粒长度。因此,我们的研究结果揭示了GDF11的功能,并为GDF11在衰老中的作用提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/722e/9055169/10e72048c8c8/j_biol-2022-0044-fig001.jpg

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