Ring finger protein 10 improves pirarubicin-induced cardiac inflammation by regulating the AP-1/Meox2 signaling pathway

作者全名："Duan, Liang; Tang, Heng; Lan, Ying; Shi, Hongwei; Pu, Peng; He, Quan"

作者地址："[Duan, Liang; Tang, Heng; Pu, Peng; He, Quan] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, 1 Youyi Rd, Chongqing 400042, Peoples R China; [Lan, Ying] Chengdu Univ, Affiliated Hosp, Dept Crit Care Med, Chengdu, Sichuan, Peoples R China; [Shi, Hongwei] Huazhong Univ Sci & Technol, Hubei Canc Hosp, Tongji Med Coll, Dept Radiat Oncol, Wuhan, Peoples R China; [Shi, Hongwei] Wuhan Univ, Renmin Hosp, Dept Oncol, Wuhan, Peoples R China"

通信作者："He, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, 1 Youyi Rd, Chongqing 400042, Peoples R China."

来源：TOXICOLOGY AND APPLIED PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000975697600001

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：462

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Pirarubicin; RNF10; Meox2; Cardiac inflammation; AP-1

摘要："Objectives: Pirarubicin (THP) is widely used in clinical antitumor therapy, but its cardiotoxicity seriously affects the therapeutic effect in patients. In the study, we investigated the role of ring finger protein 10 (RNF10) in cardiotoxicity induced by THP. Materials and methods: A cardiac toxicity model in Sprague-Dawley (SD) rats induced by THP was established. Changes in diet, weight, electrocardiogram (ECG), and echocardiography were observed. Serum levels of brain natriuretic peptide (BNP), creatine kinase MB (CK-MB), cardiac troponin T (cTnT), and lactate dehydrogenase (LDH) were measured. The expression of RNF10 in myocardium was observed by immunohistochemistry. The expressions of RNF10, activator protein-1 (AP-1), mesenchyme homeobox 2 (Meox2), total nuclear factor (NF)kappa B p65 (T-P65), phosphorylated NF-kappa B p65 (P-P65), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and mature IL-1 beta were detected by Western blot. A THP-induced H9c2 myocardial cell injury model was established. RNF10 was downregulated or overexpressed by RNF10 siRNA and a RNF10 lentiviral vector, respectively. Then, cell viability was measured. The expression of RNF10 in H9c2 cells was observed by immunofluorescence. All of the above signaling pathways were verified by Western blots. Findings: THP caused a series of cardiotoxic manifestations in SD rats. Our studies suggested that THP caused cardiac inflammation by inhibiting the expression of RNF10, while overexpression of RNF10 antagonized the cardiotoxicity induced by THP. Significance: Our study showed RNF10 improved THP-induced cardiac inflammation by regulating the AP-1/ Meox2 signaling pathway. RNF10 may be a new target to treat THP-induced cardiotoxicity."

基金机构："National Key Research and Devel- opment Program of China [2018YFC1311400, 2018YFC1311404]"

基金资助正文："Funding This work was supported by the National Key Research and Devel- opment Program of China (2018YFC1311400, 2018YFC1311404) ."