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转录组学和蛋白质组学分析揭示了盲鼹鼠细胞衰老过程中的JAK信号传导和炎症表型:卓越生物学的体现

Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology.

作者信息

Inci Nurcan, Akyildiz Erdogan Oguzhan, Bulbul Abdullah Alper, Turanli Eda Tahir, Akgun Emel, Baykal Ahmet Tarik, Colak Faruk, Bozaykut Perinur

机构信息

Department of Molecular and Translational Biomedicine, Institute of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey.

Department of Biostatistics and Bioinformatics, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey.

出版信息

Biology (Basel). 2022 Aug 23;11(9):1253. doi: 10.3390/biology11091253.

Abstract

The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK-STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated / expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK-STAT signaling were upregulated in the late passage cells, while some other cytokines such as MMPs and SERPINs were downregulated, representing a possible balance of senescence-associated secretory phenotypes (SASPs) in the BMR. Finally, our proteomics data also confirmed cytokine-mediated signaling activation in senescent BMR fibroblasts. Together, our findings suggest the critical role of JAK-STAT and cytokine-mediated signaling pathways during cellular senescence, pointing to the possible contribution of divergent inflammatory factors to the superior resistance of aging and cancer in BMRs.

摘要

盲鼹鼠(BMR)是一种寿命较长的地下啮齿动物,是衰老和癌症研究的杰出模型,因为它们不会表现出与年龄相关的表型或肿瘤形成。Janus激酶-信号转导子和转录激活子(JAK-STAT)信号通路是一种细胞因子刺激的途径,在免疫调节、增殖和细胞因子产生中起关键作用。因此,该途径最近在细胞衰老研究中引起了关注。在这里,通过使用公开可用的数据,我们报告与小鼠相比,BMR中的JAK-STAT信号被抑制。有趣的是,我们的实验结果表明,在复制性衰老过程中,BMR成纤维细胞中的/表达上调。使用公开可用数据进行的转录组分析还表明,与JAK-STAT信号相关的各种细胞因子在传代后期细胞中上调,而其他一些细胞因子如基质金属蛋白酶(MMPs)和丝氨酸蛋白酶抑制剂(SERPINs)则下调,这代表了BMR中衰老相关分泌表型(SASPs)的一种可能平衡。最后,我们的蛋白质组学数据也证实了衰老的BMR成纤维细胞中细胞因子介导的信号激活。总之,我们的研究结果表明JAK-STAT和细胞因子介导的信号通路在细胞衰老过程中起关键作用,指出不同炎症因子可能对BMR中衰老和癌症的超强抗性有贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2979/9495822/853f0e28c25a/biology-11-01253-g001.jpg

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