Serotonin receptor subtype-2B signaling is associated with interleukin-18-induced cardiomyoblast hypertrophy in vitro.

IF 0.4 4区医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Asian Biomedicine Pub Date : 2022-04-01 DOI:10.2478/abm-2022-0010

Chao-Yi Chen, Jyh-Gang Leu, Kuan-Yu Lin, Chin-Yu Shih, Yao-Jen Liang

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Abstract

Background: In patients with heart failure, interleukin-18 (IL-18) levels increase in the circulatory system and injured myocardial tissue. Serotonin (5-hydroxytryptamine) receptors subtype 2B (HTR2B) play an essential role in cardiac function and development, and their overexpression in rats leads to myocardial hypertrophy. Epigallocatechin gallate (EGCG) is cardioprotective in myocardial ischemia-reperfusion injury in rats and can prevent pressure overload-mediated cardiac hypertrophy in vivo. Mice deficient in peroxisome proliferator-activated receptor delta (PPARδ) can have cardiac dysfunction, myocardial hypertrophy, and heart failure. Matrix metalloproteinases (MMPs) are possibly involved in cardiac remodeling. However, the relationship between IL-18 signaling, cardiac hypertrophy, and the molecular mechanisms involved remain to be fully elucidated.

Objectives: To elucidate the relationship between HTR2B and IL-18-induced myocardial hypertrophy and examine the antihypertrophic effects of EGCG and PPARδ.

Methods: We induced H9c2 cardiomyoblast hypertrophy with IL-18 in vitro and investigated the downstream signaling by real-time polymerase chain reaction (PCR) and western blotting. Hypertrophy was assessed by flow cytometry. We determined the effects of EGCG and PPARδ on IL-18-induced hypertrophic signaling via HTR2B-dependent mechanisms.

Results: IL-18-induced H9c2 hypertrophy upregulated brain natriuretic peptide (BNP) protein and mRNA expression by inducing the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the hypertrophy was attenuated by pretreatment with EGCG (20 μM) and L-165,041 (2 μM), a PPARδ agonist. IL-18 upregulated the expression of HTR2B, which was inhibited by pretreatment with EGCG and L-165,041. SB215505 (0.1 μM), a HTR2B antagonist and siRNA for HTR2B, attenuated H9c2 hypertrophy significantly. Inhibition of HTR2B also downregulated the expression of MMP-3 and MMP-9.

Conclusions: IL-18 and HTR2B play critical roles in cardiomyoblast hypertrophy. EGCG and L-165,041 inhibit the expression of HTR2B and augment remodeling of H9c2 cardiomyoblasts, possibly mediated by MMP-3 and MMP-9.

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血清素受体亚型2b信号传导与白细胞介素18诱导的体外成心肌细胞肥大有关。

背景:在心力衰竭患者中，循环系统和受损心肌组织中的白细胞介素-18 (IL-18)水平升高。血清素(5-羟色胺)受体2B亚型(HTR2B)在心脏功能和发育中起重要作用，其在大鼠中的过度表达可导致心肌肥大。表没食子儿茶素没食子酸酯(EGCG)在大鼠心肌缺血再灌注损伤中具有心脏保护作用，可在体内预防压力过载介导的心肌肥厚。缺乏过氧化物酶体增殖物激活受体δ (PPARδ)的小鼠可出现心功能障碍、心肌肥厚和心力衰竭。基质金属蛋白酶(MMPs)可能参与心脏重构。然而，IL-18信号传导与心肌肥厚之间的关系及其分子机制仍未完全阐明。目的:探讨HTR2B与il -18诱导心肌肥厚的关系，探讨EGCG和PPARδ的抗肥厚作用。方法:用IL-18体外诱导H9c2成心肌细胞肥厚，采用实时聚合酶链反应(PCR)和western blotting检测下游信号通路。流式细胞术检测肥厚。我们通过htr2b依赖机制确定了EGCG和PPARδ对il -18诱导的肥厚信号传导的影响。结果:il -18诱导的H9c2肥厚通过诱导活化B细胞核因子κB轻链增强子(NF-κB)的表达上调脑钠肽(BNP)蛋白和mRNA的表达，EGCG (20 μM)和PPARδ激动剂L-165,041 (2 μM)预处理可减轻肥厚。IL-18上调HTR2B的表达，EGCG和L-165,041预处理可抑制HTR2B的表达。HTR2B拮抗剂和HTR2B siRNA SB215505 (0.1 μM)可显著减轻H9c2的肥厚。抑制HTR2B还可下调MMP-3和MMP-9的表达。结论:IL-18和HTR2B在成心肌细胞肥厚中起重要作用。EGCG和L-165,041抑制HTR2B的表达，增强H9c2心肌细胞的重塑，可能是由MMP-3和MMP-9介导的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Asian Biomedicine 医学-医学：研究与实验

CiteScore

1.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Asian Biomedicine: Research, Reviews and News (ISSN 1905-7415 print; 1875-855X online) is published in one volume (of 6 bimonthly issues) a year since 2007. [...]Asian Biomedicine is an international, general medical and biomedical journal that aims to publish original peer-reviewed contributions dealing with various topics in the biomedical and health sciences from basic experimental to clinical aspects. The work and authorship must be strongly affiliated with a country in Asia, or with specific importance and relevance to the Asian region. The Journal will publish reviews, original experimental studies, observational studies, technical and clinical (case) reports, practice guidelines, historical perspectives of Asian biomedicine, clinicopathological conferences, and commentaries Asian biomedicine is intended for a broad and international audience, primarily those in the health professions including researchers, physician practitioners, basic medical scientists, dentists, educators, administrators, those in the assistive professions, such as nurses, and the many types of allied health professionals in research and health care delivery systems including those in training.