Troxerutin attenuates myocardial cell apoptosis following myocardial ischemia‐reperfusion injury through inhibition of miR‐146a‐5p expression

Shu, Liliang; Zhang, Wanzhe; Huang, Guofu; Huang, Chen; Zhu, Xiaohua; Su, Gang; Xu, Jing

doi:10.1002/jcp.27607

Cited by 28 publications

(29 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Suppression of miR-146a-5p in mesenchymal stem cells (MSCs) inhibited their proliferation but promoted their migration, suggesting that miR-146a-5p is crucial to uncouple the direct effects of proliferation and motility of MSCs [32]. Our study together with several previous studies [16, 30] suggested that miR-146a-5p also could mediate IH-induced injury in H9c2 cells.…”

Section: Discussionsupporting

confidence: 68%

“…Recently, miR-146a-5p has been verified as a crucial regulator in the development of numerous cancers such as breast cancer [13], prostate cancer [14], and gastric cancer [15]. Furthermore, miR-146a-5p was upregulated in the myocardial hypoxia/reoxygenation (H/R) cell model and rat model of ischemia/reperfusion (I/R), while troxerutin could exert cardioprotective effects on H/R cells and I/R-injured rats by downregulation of miR-146a-5p [16]. However, the effects and modulatory mechanism of miR-146a-5p in protecting cardiomyocytes from IH-induced injury have not been studied.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

miR-146a-5p Mediates Intermittent Hypoxia-Induced Injury in H9c2 Cells by Targeting XIAP

Lin

Huang

Chen

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

MicroRNAs (miRNAs) have emerged as key modulators in the pathophysiologic processes of cardiovascular diseases. However, its function in cardiac injury induced by obstructive sleep apnea (OSA) remains unknown. The aim of the current study was to identify the effect and potential molecular mechanism of miR-146a-5p in intermittent hypoxia(IH)- induced myocardial damage. We exposed H9c2 cells to IH condition; the expression levels of miR-146a-5p were detected by RT-qPCR. Cell viability, cell apoptosis, and the expressions of apoptosis-associated proteins were assessed via Cell Counting Kit-8 (CCK-8), flow cytometry, and western blotting, respectively. Target genes of miR-146a-5p were confirmed by dual-luciferase reporter assay. IH remarkably lowered viability but enhanced cell apoptosis. Concomitantly, the miR-146a-5p expression level was increased in H9c2 cells after IH. Subsequent experiments showed that IH-induced injury was alleviated through miR-146a-5p silence. X-linked inhibitor of apoptosis protein (XIAP) was predicted by bioinformatics analysis and further confirmed as a direct target gene of miR-146a-5p. Surprisingly, the effect of miR-146a-5p inhibition under IH may be reversed by downregulating XIAP expression. In conclusion, our results demonstrated that miR-146a-5p could attenuate viability and promote the apoptosis of H9c2 by targeting XIAP, thus aggravating the H9c2 cell injury induced by IH, which could enhance our understanding of the mechanisms for OSA-associated cardiac injury.

show abstract

Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

miR-146a-5p Mediates Intermittent Hypoxia-Induced Injury in H9c2 Cells by Targeting XIAP

Lin

Huang

Chen

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Notably, this negative effect of SFN was maintained in the S. aureus-infected Nrf2 -/-BMdM. The expression levels of miR-142-5p and miR-146a-5p have been associated with cell apoptosis (26,27). Therefore, the effects of SFN on the levels of these miRNAs were examined.…”

Section: Sfn Affects Intracellular S Aureus Survival and Cell Apoptosismentioning

confidence: 99%

Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation

Deramaudt¹,

Ali²,

Vinit³

et al. 2020

Int J Mol Med

View full text Add to dashboard Cite

Macrophages are active contributors to the innate immune defense system. As macrophage activation is clearly affected by the surrounding microenvironment, the present study investigated the effect of sulforaphane (SFN) on the bactericidal activity of macrophages and the underlying molecular mechanisms involved in this process. Human THP-1-derived macrophages, primary human peripheral blood mononuclear cell-derived macrophages, and primary mouse bone marrow derived-macrophages (BMdMs) pretreated with SFN or dMSO were utilized in a model of Staphylococcus aureus infection. The results suggested that SFN pretreatment of macrophages effectively repressed the intracellular survival of S. aureus through modulation of p38/JNK signaling and decreased S. aureus-induced caspases-3/7-dependent cell apoptosis, potentially through downregulation of microRNA (miR)-142-5p and miR-146a-5p. As SFN is a well-known activator of nuclear factor erythroid 2-related factor 2 (Nrf2), Nrf2 -/-BMdMs were used to demonstrate that the SFN-mediated inhibitory effect was independent of Nrf2. Nevertheless, an increase in intracellular bacterial survival in Nrf2-deficient macrophages was observed. In addition, SFN pretreatment suppressed S. aureus-induced transcriptional expression of genes coding for the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), as well as for the M1 markers c-c motif chemokine receptor 7, IL-23 and inducible nitric oxide synthase (iNOS). Western blot analysis indicated that S. aureus challenge activated p38 mitogen-activated protein kinase (MAPK) (p38) and c-Jun N-terminal kinase (JNK) MAPK signaling pathways, while SFN pretreatment prevented p38 and JNK phosphorylation. Pretreatment with 2 specific inhibitors of p38 and JNK, SB203580 and SP600125, respectively, resulted in a decrease in S. aureus-induced proinflammatory gene expression levels compared with those observed in the SFN-pretreated macrophages. Furthermore, THP-1-derived macrophages pretreated with SB203580 or SP600125 prior to bacterial infection exhibited a significant inhibition in intracellular S. aureus survival.In conclusion, we hypothesize that concomitant targeting of the p38/JNK-inflammatory response and the S. aureus-induced apoptosis with SFN may be a promising therapeutic approach in S. aureus infection.

show abstract

“…However, one must not overlook their pro-survival effects that could elicit, for example, an adverse fibrotic response or a worsened diabetic retinopathy [108,118,119,120,121]. Indeed, this becomes important since it was very recently shown that downregulating miR-146a-5p may be needed in alleviating I/R injury [122]. Therefore, additional research is still required to better elaborate on the effects of individual and synergetic application of these miRNAs.…”

Section: Micrornas (Mirnas)mentioning

confidence: 99%

MicroRNAs as Potential Pharmaco-Targets in Ischemia-Reperfusion Injury Compounded by Diabetes

Dehaini

Awada

El‐Yazbi

et al. 2019

Cells

View full text Add to dashboard Cite

Background: Ischemia-Reperfusion (I/R) injury is the tissue damage that results from re-oxygenation of ischemic tissues. There are many players that contribute to I/R injury. One of these factors is the family of microRNAs (miRNAs), which are currently being heavily studied. This review aims to critically summarize the latest papers that attributed roles of certain miRNAs in I/R injury, particularly in diabetic conditions and dissect their potential as novel pharmacologic targets in the treatment and management of diabetes. Methods: PubMed was searched for publications containing microRNA and I/R, in the absence or presence of diabetes. All papers that provided sufficient evidence linking miRNA with I/R, especially in the context of diabetes, were selected. Several miRNAs are found to be either pro-apoptotic, as in the case of miR-34a, miR-144, miR-155, and miR-200, or anti-apoptotic, as in the case of miR-210, miR-21, and miR-146a. Here, we further dissect the evidence that shows diverse cell-context dependent effects of these miRNAs, particularly in cardiomyocytes, endothelial, or leukocytes. We also provide insight into cases where the possibility of having two miRNAs working together to intensify a given response is noted. Conclusions: This review arrives at the conclusion that the utilization of miRNAs as translational agents or pharmaco-targets in treating I/R injury in diabetic patients is promising and becoming increasingly clearer.

show abstract

Troxerutin attenuates myocardial cell apoptosis following myocardial ischemia‐reperfusion injury through inhibition of miR‐146a‐5p expression

Cited by 28 publications

References 29 publications

miR-146a-5p Mediates Intermittent Hypoxia-Induced Injury in H9c2 Cells by Targeting XIAP

miR-146a-5p Mediates Intermittent Hypoxia-Induced Injury in H9c2 Cells by Targeting XIAP

Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation

MicroRNAs as Potential Pharmaco-Targets in Ischemia-Reperfusion Injury Compounded by Diabetes

Contact Info

Product

Resources

About