RETRACTED ARTICLE: Protective functions of myricetin in LPS-induced cardiomyocytes H9c2 cells injury by regulation of MALAT1

Jinliang Sun,Jianhui Sun,Xuezhong Zhou

doi:10.1186/s40001-019-0378-5

Abstract

BackgroundMetastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a crucial mediator in response to inflammation. Myricetin protects cardiomyocytes against inflammatory injury. However, it’s still unexplored whether myricetin exerted anti-inflammatory properties via MALAT1. The purpose of our study was to validate the cardio-protective function of myricetin against myocarditis and its underlying mechanism in vitro.MethodsH9c2 cells were pre-incubated with myricetin before stimulation with lipopolysaccharide (LPS). Enforced silence of MALAT1 was achieved by transducing short hairpin (sh)-MALAT1 into H9c2 cells. Next, cell viability and apoptotic cells were detected with cell counting kit-8 (CCK-8) and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) apoptosis detection kit, respectively. Western blot assay was conducted to examine apoptosis-relative proteins, pro-inflammatory factors, and signaling regulators. Quantitative real-time PCR (qRT-PCR) was performed to quantify pro-inflammatory factors and MALAT1 at mRNA levels. Enzyme-linked immune sorbent assay (ELISA) was employed to determine protein concentration of pro-inflammatory factors.ResultsMyricetin ameliorated LPS-elicited reduction of cell viability, augment of apoptosis, and overexpression of monocyte chemo-attractant protein-1 (MCP-1) and interleukin-6 (IL-6) in H9c2 cells. Meanwhile, phosphorylation of p65 and inhibitor of nuclear factor kappa B alpha (IκBα) were suppressed. Besides, myricetin enhanced the expression of MALAT1 which was originally down-regulated by LPS. However, the protective effects of myricetin against LPS-caused inflammatory lesions were abrogated in MALAT1-deficiency cells, with the restored phosphorylation of p65 and IκBα.ConclusionMyricetin possessed an anti-inflammatory function against LPS-induced lesions in cardiomyocytes. Mechanically, myricetin up-regulated MALAT1, blocked LPS-evoked activation of nuclear factor-κB (NF-κB) inflammatory pathway, and, finally, exerted cardio-protective effects.

Highlights

Myocarditis has been defined as the manifestations of pathological immune processes in the clinic and histology
LPS extremely accelerated the apoptosis of H9c2 cells (P < 0.001) (Fig. 3b), which was further indicated by the increased expression of cleaved caspase-3 and Bax as well as the decreased level of Bcl-2 (Fig. 3c)
The evident decline of monocyte chemo-attractant protein-1 (MCP-1) and IL-6 (P < 0.05 or P < 0.01), at mRNA (Fig. 4d) and protein (Fig. 4e–f ) levels, was observed in myricetin pre-incubated H9c2 cells. These results potentially implied that myricetin protected cardiomyocytes H9c2 cells against LPS-induced inflammatory injury

Summary

Introduction

Myocarditis has been defined as the manifestations of pathological immune processes in the clinic and histology. Persistent myocarditis potentially contributes to the structural and functional abnormalities in cardiomyocytes, which. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), as a long non-coding RNA (lncRNA), has been found to participate in mediating. The inflammation-regulatory function of MALAT1 might be attributed to its modulation on NF-κB. A recent study suggested that MALAT1 interacts with NF-κB in the nucleus, to inhibit its DNA-binding activity, and, to retard the expression of inflammatory cytokines [9]. MALAT1 inhibits hypoxiainduced inflammatory response through NF-κB signaling pathway in the renal ischemia–reperfusion injury [10]. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a crucial mediator in response to inflammation. The purpose of our study was to validate the cardio-protective function of myricetin against myocarditis and its underlying mechanism in vitro

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