CIRBP-OGFR axis safeguards against cardiomyocyte apoptosis and cardiotoxicity induced by chemotherapy.
CIRBP-OGFR axis safeguards against cardiomyocyte apoptosis and cardiotoxicity induced by chemotherapy.
复制标题
CIRBP-OGFR 轴可防止化疗引起的心肌细胞凋亡和心脏毒性
DOI：
10.7150/ijbs.69655
复制
发表时间：
2022
影响因子：
9.2
通讯作者：
Tang, Hao
中科院分区：
文献类型：
--
作者：
Liu, Cihang;Cheng, Xiaolei;Xing, Junyue;Li, Jun;Li, Zhen;Jian, Dongdong;Wang, Ying;Wang, Shixing;Li, Ran;Zhang, Wanjun;Shao, Dongxing;Ma, Xiaohan;Chen, Xiru;Shen, Jia;Shi, Chao;Guo, Zhiping;Wang, Wengong;Fan, Taibing;Liu, Lin;Tang, Hao
冷诱导rna结合蛋白（CIRBP）是维持心脏功能所必需的，然而，其在化疗诱导的心脏毒性中的作用仍然不清楚。在此，我们报道了CIRBP通过破坏OGF-OGFR信号减少心肌细胞凋亡和减弱心脏毒性。CIRBP缺乏与多种化疗药物诱导的心肌细胞凋亡有关。向小鼠心肌输送外源性CIRBP可显著减轻阿霉素诱导的心脏凋亡和功能障碍。具体而言，OGFR被确定为下游核心效应负责化疗诱导的心肌细胞凋亡。CIRBP被证明与OGFR mRNA相互作用，并通过降低mRNA稳定性抑制OGFR表达。CIRBP介导的对阿霉素诱导的心脏凋亡的细胞保护主要涉及CIRBP对OGFR的抑制。NTX作为一种有效的OGFR拮抗剂，成功地挽救了暴露于阿霉素后CIRBP消融导致的心脏不平衡易感性，而另一种拮抗剂ALV仅作用于阿片受体却没有。综上所述，我们的研究结果表明，CIRBP通过抑制OGF/OGFR轴，赋予心肌对化疗诱导的心脏凋亡和功能障碍的抗性，为化疗诱导的心脏毒性机制提供了新的视角，并为癌症患者开发有效的心脏保护策略提供了见解。
Cold-inducible RNA-binding protein (CIRBP) is documented to be required for maintaining cardiac function, however, its role in chemotherapy-induced cardiotoxicity remains obscured. Herein, we report that CIRBP decreases cardiomyocyte apoptosis and attenuates cardiotoxicity through disrupting OGF-OGFR signal. CIRBP deficiency is involved in diverse chemotherapeutic agents induced cardiomyocyte apoptosis. Delivery of exogenous CIRBP to the mouse myocardium significantly mitigated doxorubicin-induced cardiac apoptosis and dysfunction. Specifically, OGFR was identified as a downstream core effector responsible for chemotherapy-induced cardiomyocyte apoptosis. CIRBP was shown to interact with OGFR mRNA and to repress OGFR expression by reducing mRNA stability. CIRBP-mediated cytoprotection against doxorubicin-induced cardiac apoptosis was demonstrated to largely involve OGFR repression by CIRBP. NTX as a potent antagonist of OGFR successfully rescued CIRBP ablation-rendered susceptibility to cardiac dyshomeostasis upon exposure to doxorubicin, whereas another antagonist ALV acting only on opioid receptors did not. Taken together, our results demonstrate that CIRBP confers myocardium resistance to chemotherapy-induced cardiac apoptosis and dysfunction by dampening OGF/OGFR axis, shedding new light on the mechanisms of chemo-induced cardiotoxicity and providing insights into the development of an efficacious cardioprotective strategy for cancer patients.
登录
查看更多内容
影响因子：
14.9
作者：
Solano-Gonzalez E;Coburn KM;Yu W;Wilson GM;Nurmemmedov E;Kesari S;Chang ET;MacKerell AD;Weber DJ;Carrier F
通讯作者：
Carrier F
影响因子：
37.3
作者：
Cheng, Fan;McLaughlin, Patricia J.;Zagon, Ian S.
通讯作者：
Zagon, Ian S.
影响因子：
14.9
作者：
Ma J;Chen T;Wu S;Yang C;Bai M;Shu K;Li K;Zhang G;Jin Z;He F;Hermjakob H;Zhu Y
通讯作者：
Zhu Y
DOI：
10.1016/j.bbrc.2015.07.066
发表时间：
2015-08-28
影响因子：
3.1
作者：
Lee, Hae Na;Ahn, Sung-Min;Jang, Ho Hee
通讯作者：
Jang, Ho Hee
DOI：
10.1016/j.bbamcr.2006.02.007
发表时间：
2006-03-01
影响因子：
5.1
作者：
Sakurai, Toshiharu;Itoh, Katsuhiko;Fujita, Jun
通讯作者：
Fujita, Jun