EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50

	EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50
	Li, KQ; Liu, GJ; Liu, XY; Chen, QF; Huang, XY; Tu, Q; Zhang, J; Chang, Q; Xie, YH; Hua, R; Xu, DM; Liu, Z; Zhao, B
	2023
发表期刊	ZOOLOGICAL RESEARCH
ISSN	2095-8137
卷号	44 期号:3 页码:636+
摘要	Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As relatively long-lived mammals based on body size, bats display unique telomeric patterns, including the up -regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion. Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro-cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans. In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism forregulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14135
专题	科研部门_进化发育生物学（刘振）
推荐引用方式 GB/T 7714	Li, KQ,Liu, GJ,Liu, XY,et al. EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50[J]. ZOOLOGICAL RESEARCH,2023,44(3):636+.
APA	Li, KQ.,Liu, GJ.,Liu, XY.,Chen, QF.,Huang, XY.,...&Zhao, B.(2023).EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50.ZOOLOGICAL RESEARCH,44(3),636+.
MLA	Li, KQ,et al."EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50".ZOOLOGICAL RESEARCH 44.3(2023):636+.

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