Kansere ve yaşlanmaya karşı üstün dirençli farelerde Nrf2 yolağını düzenleyen faktörlerin transkriptomik düzeyde analizi

Amaç: Çıplak Kör Fareler (ÇKF), 30 yılı aşkın sıra dışı uzun yaşam sürelerine sahip olmaları ve bu uzun yaşamları boyunca kanser gelişimi göstermemeleri ile biyomedikal araştırmalarda kullanılmaktadır. Yapılan çalışmalar, ÇKF’lerin üstün bir stres direncine sahip olduğunu ve temel bir oksidatif stres mekanizması olan Nükleer faktör-eritroit 2 ilişkili faktör (Nrf2) sinyal yolağının önemli bir rolü olduğunu göstermektedir. ÇKF’leri stresten koruyan başka bir mekanizmanın ise sağlık alanında sıklıkla kullanılan kök hücreler olduğu düşünülmektedir. Bu sebeplerden dolayı yapılan çalışmanın amacı, kör farelerin fibroblast ve indüklenmiş pluripotent kök hücrelerinde Nrf2 ekspresyonunu düzenleyen faktörlerin tayin edilmesidir. Yöntem: ÇKF’ler ve laboratuvar farelerinin (Mus musculus) RNA sekanslama metodu ile elde edilen transkriptom verileri kıyaslamalı olarak analiz edildi. Bu 2 türe ait fibroblast ve indüklenmiş pluripotent kök hücrelerine ait veriler spesifik olarak Nrf2 aktivatörleri (Dpp3, Sqstm1, Palb2, Amer1, Mapk14, Trp53) ve inhibitorleri (Keap1, Siah1, Btrc) olarak kabul edilen genler açısından incelendi. Bulgular: Elde edilen bulgular, ÇFK hücrelerinde Nrf2 aktivatör ve inhibitör adayları arasındaki RNA ekspresyonları değişimlerini gösterdi. Fare fibroblast hücrelerine kıyaslandığında, ÇKF fibroblast hücrelerinde Nrf2 aktivatörü olarak kabul edilen Palb2 RNA ekspresyonunda önemli düzeyde artış (p

Transcriptomics Analysis of Nrf2 Regulators in Cancer Resistant and Long-Lived Naked Mole-Rats

Purpose: Naked mole-rats (NMR, Heterocephalus glaber) have extreme resistance to cancer although they are known as the longest-living rodent with their 30-year maximum lifespan. Therefore, NMRs have rapidly emerged as a natural model for biomedical research. Studies have shown that NMRs can better tolerate stress due to mechanisms, such as upregulation of the Nrf2 pathway. Another mechanism proposed to contribute to their protection from stress involves stem cells. Therefore, in this study, we aimed to identify the regulation of Nrf2 signaling in NMR fibroblasts and induced pluripotent stem cells (iPSCs). Methods: The transcriptomics data of NMR and laboratory mice (Mus musculus) were used in the study. Particularly, the genes that are accepted as Nrf2 activators (Dpp3, Sqstm1, Palb2, Amer1, Mapk14, Trp53) and inhibitors (Keap1, Siah1, Btrc) were comparatively analyzed in fibroblasts and iPSCs of both species. Results: Our data demonstrated differentially expressed gene expressions between different cell types. Among target Nrf2 activators, Palb2 RNA expression was found to be increased significantly (p

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