Dataset Information

Zinc Finger Protein ZBTB20 protects against cardiac remodelling post-myocardial infarction via ROS-TNF?/ASK1/JNK pathway regulation.

ABSTRACT: This study aims to determine the efficacy of Zinc finger protein ZBTB20 in treatment of post-infarction cardiac remodelling. For this purpose, left anterior descending (LAD) ligation was operated on mice to induce myocardial infarction (MI) with sham control group as contrast and adeno-associated virus (AAV9) system was used to deliver ZBTB20 to mouse heart by myocardial injection with vehicle-injected control group as contrast two weeks before MI surgery. Then four weeks after MI, vehicle-treated mice with left ventricular (LV) remodelling underwent deterioration of cardiac function, with symptoms of hypertrophy, interstitial fibrosis, inflammation and apoptosis. The vehicle-injected mice also showed increase of infarct size and decrease of survival rate. Meanwhile, the ZBTB20-overexpressed mice displayed improvement after MI. Moreover, the anti-apoptosis effect of ZBTB20 was further confirmed in H9c2 cells subjected to hypoxia in vitro. Further study suggested that ZBTB20 exerts cardioprotection by inhibiting tumour necrosis factor ?/apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase 1/2 (JNK1/2) signalling, which was confirmed by shRNA-JNK adenoviruses transfection or a JNK activator in vitro as well as ASK1 overexpression in vivo. In summary, our data suggest that ZBTB20 could alleviate cardiac remodelling post-MI. Thus, administration of ZBTB20 can be considered as a promising treatment strategy for heart failure post-MI. Significance Statement: ZBTB20 could alleviate cardiac remodelling post-MI via inhibition of ASK1/JNK1/2 signalling.

SUBMITTER: Li F

PROVIDER: S-EPMC7701508 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Zinc Finger Protein ZBTB20 protects against cardiac remodelling post-myocardial infarction via ROS-TNFα/ASK1/JNK pathway regulation.

Li Fangfang F Yang Yiming Y Xue Chuanyou C Tan Mengtong M Xu Lu L Gao Jianbo J Xu Luhong L Zong Jing J Qian Wenhao W

Journal of cellular and molecular medicine 20201016 22

This study aims to determine the efficacy of Zinc finger protein ZBTB20 in treatment of post-infarction cardiac remodelling. For this purpose, left anterior descending (LAD) ligation was operated on mice to induce myocardial infarction (MI) with sham control group as contrast and adeno-associated virus (AAV9) system was used to deliver ZBTB20 to mouse heart by myocardial injection with vehicle-injected control group as contrast two weeks before MI surgery. Then four weeks after MI, vehicle-treat ...[more]

PMID: 33063955

Similar Datasets

Project description:A unique feature of CD40 among the TNF receptor (TNFR) superfamily is its exquisitely contextual effects, as originally demonstrated in normal and malignant B-lymphocytes. We studied renal cell carcinoma (RCC) in comparison to normal (human renal proximal tubule) cells, as a model to better understand the role of CD40 in epithelial cells. CD40 ligation by membrane-presented CD40 ligand (mCD40L), but not soluble CD40 agonist, induced extensive apoptosis in RCC cells; by contrast, normal cells were totally refractory to mCD40L. These findings underline the importance of CD40 'signal-quality' on cell fate and explain the lack of pro-apoptotic effects in RCC cells previously, while confirming the tumour specificity of CD40 in epithelial cells. mCD40L differentially regulated TRAF expression, causing sustained TRAF2/TRAF3 induction in RCC cells, yet downregulation of TRAF2 and no TRAF3 induction in normal cells, observations strikingly reminiscent of TRAF modulation in B-lymphocytes. mCD40L triggered reactive oxygen species (ROS) production, critical in apoptosis, and NADPH oxidase (Nox)-subunit p40phox phosphorylation, with Nox blockade abrogating apoptosis thus implying Nox-dependent initial ROS release. mCD40L mediated downregulation of Thioredoxin-1 (Trx-1), ASK1 phosphorylation, and JNK and p38 activation. Although both JNK/p38 were essential in apoptosis, p38 activation was JNK-dependent, which is the first report of such temporally defined JNK-p38 interplay during an apoptotic programme. CD40-killing entrained Bak/Bax induction, controlled by JNK/p38, and caspase-9-dependent mitochondrial apoptosis, accompanied by pro-inflammatory cytokine secretion, the repertoire of which also depended on CD40 signal quality. Previous reports suggested that, despite the ability of soluble CD40 agonist to reduce RCC tumour size in vivo via immunocyte activation, RCC could be targeted more effectively by combining CD40-mediated immune activation with direct tumour CD40 signalling. Since mCD40L represents a potent tumour cell-specific killing signal, our work not only offers insights into CD40's biology in normal and malignant epithelial cells, but also provides an avenue for a 'double-hit' approach for inflammatory, tumour cell-specific CD40-based therapy.

Dataset Information

Zinc Finger Protein ZBTB20 protects against cardiac remodelling post-myocardial infarction via ROS-TNF?/ASK1/JNK pathway regulation.

Publications

Zinc Finger Protein ZBTB20 protects against cardiac remodelling post-myocardial infarction via ROS-TNFα/ASK1/JNK pathway regulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets