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细胞衰老相关分泌表型因子及其分子调控机制研究进展
王瑜,朱振新,蔡清萍*
0
(海军军医大学(第二军医大学)长征医院普外二科, 上海 200003
*通信作者)
摘要:
细胞衰老是增殖细胞脱离细胞周期呈永久性生长停滞的状态,其显著特点之一是分泌大量生物活性物质,即细胞衰老相关分泌表型(SASP)因子。SASP因子的分泌大致可分为DNA损伤快速旁分泌期、SASP早期、SASP成熟期3个阶段。SASP因子的分子调控机制复杂,涉及DNA损伤反应、p38丝裂原活化蛋白激酶(MAPK)信号通路、核因子κB(NF-κB)及CCAAT/增强子结合蛋白β(C/EBPβ)激活、SASP基因表观遗传学改变、基因转录后调控和自噬等。SASP因子能改变细胞微环境导致的多种病理状态的发生,已成为调节衰老效应的药物靶标,为肿瘤和年龄相关性疾病提供了新的治疗方向。基于此,本文对SASP因子进行了分类,总结了其在生物过程中的作用,并深入探讨其调控机制。
关键词:  细胞衰老  衰老相关分泌表型  DNA损伤  p38蛋白  核因子κB  CCAAT/增强子结合蛋白β  表观遗传学  自噬
DOI:10.16781/j.0258-879x.2018.04.0422
投稿时间:2017-08-21修订日期:2017-12-25
基金项目:国家自然科学基金(8137260,81100629).
Senescence-associated secretory phenotype and its complex regulation networks: a review of molecular mechanisms
WANG Yu,ZHU Zhen-xin,CAI Qing-ping*
(Department of General Surgery(Ⅱ), Changzheng Hospital, Navy Medical University(Second Military Medical University), Shanghai 200003, China
*Corresponding author)
Abstract:
Cellular senescence is a state of permanent growth arrest characterized by an irreversible exit from the cell cycle and the secretion of senescence-associated secretory phenotype (SASP). The secretory process of SASP can be roughly divided into three steps:DNA damage response (DDR)-rapid paracrine, early and mature stages. The complex molecular regulation mechanisms of SASP involve DDR, p38 mitogen-activated protein kinase (MAPK) signal pathway, activation of nuclear factor κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ), epigenetic alterations of SASP gene, post-transcriptional regulation of gene and autophagy. SASP regulates a variety of pathological states caused by microenvironment changes and has been a drug target to regulate the aging effect, which providing a new therapeutic method for tumor and age-related pathological states. In this paper, we classified the different types of SASP, reviewed the role of SASP in biological processes and discussed the related molecular mechanisms.
Key words:  cell senescence  senescence-associated secretory phenotype  DNA damage  p38 protein  nuclear factor κB  CCAAT/enhancer-binding protein β  epigenetics  autophagy