2. Academic Validation
  3. Ring finger protein 10 improves pirarubicin-induced cardiac inflammation by regulating the AP-1/Meox2 signaling pathway

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

  • Toxicol Appl Pharmacol. 2023 Feb 3;462:116411. doi: 10.1016/j.taap.2023.116411.
Liang Duan 1,  Heng Tang 1,  Ying Lan 2,  Hongwei Shi 3,  Peng Pu 1,  Quan He 4
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Critical Care Medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China.
  • 3 Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 4 Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 36740146 DOI: 10.1016/j.taap.2023.116411
Abstract

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)-κB p65 (T-P65), phosphorylated NF-κB p65 (PP65), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and mature IL-1β 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.

Keywords

AP-1; Cardiac inflammation; Meox2; Pirarubicin; RNF10.

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