Modified citrus pectin ameliorates myocardial fibrosis and inflammation via suppressing galectin-3 and TLR4/MyD88/NF-κB signaling pathway

Xu, Gengrui; Zhang, Chuang; Yang, Hongxia; Sun, Jia‐Huan; Zhang, Yue; Yao, Tingting; Li, Yuan; Ruan, Linhui; An, Ran; Li, Aiying

doi:10.1016/j.biopha.2020.110071

Cited by 106 publications

(69 citation statements)

References 53 publications

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“…Inflammatory fibroblasts persistently activate the fibroblasts in an autocrine/paracrine manner in the lungs, resulting in pulmonary fibrosis (63)(64)(65). The proinflammatory role of TLR4-MD2 complex and Myd88 signaling pathway in the lungs has also been evaluated (66)(67)(68)(69) and associated with the fibrotic process leading to pulmonary fibrosis (60,(70)(71)(72)(73)(74). In our study, we found that eCIRP induces proinflammatory cytokines and their pathways in pulmonary fibroblasts in a TLR4 dependent manner.…”

Section: Discussionsupporting

confidence: 54%

Extracellular CIRP Induces an Inflammatory Phenotype in Pulmonary Fibroblasts via TLR4

2021

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Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern (DAMP), has been recently shown to play a critical role in promoting the development of bleomycin-induced pulmonary fibrosis. Although fibroblast activation is a critical component of the fibrotic process, the direct effects of eCIRP on fibroblasts have never been examined. We studied eCIRP’s role in the induction of inflammatory phenotype in pulmonary fibroblasts and its connection to bleomycin-induced pulmonary fibrosis in mice. We found that eCIRP causes the induction of proinflammatory cytokines and differentially expression-related pathways in a TLR4-dependent manner in pulmonary fibroblasts. Our analysis further showed that the accessory pathways MD2 and Myd88 are involved in the induction of inflammatory phenotype. In order to study the connection of the enrichment of these pathways in priming the microenvironment for pulmonary fibrosis, we investigated the gene expression profile of lung tissues from mice subjected to bleomycin-induced pulmonary fibrosis collected at various time points. We found that at day 14, which corresponds to the inflammatory-to-fibrotic transition phase after bleomycin injection, TLR4, MD2, and Myd88 were induced, and the transcriptome was differentially enriched for genes in those pathways. Furthermore, we also found that inflammatory cytokines gene expressions were induced, and the cellular responses to these inflammatory cytokines were differentially enriched on day 14. Overall, our results show that eCIRP induces inflammatory phenotype in pulmonary fibroblasts in a TLR4 dependent manner. This study sheds light on the mechanism by which eCIRP induced inflammatory fibroblasts, contributing to pulmonary fibrosis.

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Section: Discussionsupporting

confidence: 54%

Extracellular CIRP Induces an Inflammatory Phenotype in Pulmonary Fibroblasts via TLR4

2021

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“…As inflammatory response plays an important role in all stages of the development of MI, an increasing number of studies consider anti-inflammatory as a strategy for the treatment of MI. Xu et al (2020) demonstrated that the Gal-3 inhibitor modified citrus pectin ameliorated cardiac dysfunction, decreased myocardial injury and reduced collagen deposition through inhibiting inflammation. Liu et al (2019) found that fisetin treatment improved cardiac function, inhibited macrophage recruitment into the left atrium and production of interleukin-1b (IL-1b) and tumour necrosis factor-a (TNF-a), and attenuated adverse atrial fibrosis following acute myocardial infarction.…”

Section: Discussionmentioning

confidence: 98%

Latifolin protects against myocardial infarction by alleviating myocardial inflammatory via the HIF-1α/NF-κB/IL-6 pathway

Lai

Zhang

Chen

et al. 2020

Pharmaceutical Biology

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Context: The Traditional Chinese herb medicine Dalbergia odorifera T. Chen (Fabaceae), exerted a protective effect on myocardial ischaemia. Latifolin is a neoflavonoid extracted from Dalbergia odorifera. It has been reported to have the effects of anti-inflammation and cardiomyocyte protection. Objective: To investigate whether latifolin can improve myocardial infarction (MI) through attenuating myocardial inflammatory and to explore its possible mechanisms. Materials and methods: Left coronary artery was ligated to induce a rat model of MI, and the rats were treated with sodium carboxymethyl cellulose (CMC-Na) or different doses of latifolin (25, 50, 100 mg/kg/d) by oral gavage for 28 days. Serum contents of myocardial enzyme were measured at seven and fourteen days after treatment. Cardiac function, infarct size, histopathological changes and inflammatory cells infiltration was assessed at 28 days after treatment. Western blotting was used to investigate the underlying mechanisms. Results: Latifolin treatment markedly decreased the contents of myocardial enzymes, and increased left ventricular ejection fraction (85.27% vs. 59.11%) and left ventricular fractional shortening (62.71% vs. 45.53%). Latifolin was found to significantly reduced infarction size (27.78% vs. 39.07%), myocardial fibrosis and the numbers of macrophage infiltration (436 cells/mm 2 vs. 690 cells/mm 2). In addition, latifolin down-regulated the expression levels of hypoxia-inducible factor-1a (0.95-fold), phospho-nuclear factor-jB (0.2-fold) and interleukin-6 (1.11-fold). Discussion and conclusions: Latifolin can protect against myocardial infarction by improving myocardial inflammation through the HIF-1a/NF-jB/IL-6 signalling pathway. Accordingly, latifolin may be a promising drug for pharmacological treatment of ischaemic cardiovascular disease.

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“…TAK1 activates the complex of inhibitory κB (IκB) kinase α (IKKα) and induces IκB phosphorylation (Kawai & Akira, 2010; Liu et al., 2015), and degradation of IκB in the proteasome. NF‐κB is released from the NF‐κB complex and translocated to the nucleus (Xu et al., 2020). The activation of the TLR4/MyD88 signaling pathway activates NF‐κB and contributes to the secretion of pro‐inflammatory cytokines related to AMI.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV prevents acute myocardial infarction by inhibiting the TLR4/MyD88/NF‐κB signaling pathway

et al. 2021

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Although astragaloside IV protects from acute myocardial infarction (AMI)‐induced chronic heart failure (CHF), the underlying mechanism of action is unclear. We determined the potential therapeutic effect of astragaloside IV using molecular docking approaches and validated the findings by the ligation of the left anterior descending (LAD) coronary artery‐induced AMI rat model. The interaction between astragaloside IV and myeloid differentiation factor 88 (MyD88) was evaluated by SwissDock. To explore the mechanisms underlying the beneficial effects of astragaloside IV in the LAD coronary artery ligation‐induced AMI model, we administered the rats with astragaloside IV for 4 weeks. Hemodynamic indexes were used to evaluate the degree of myocardial injury in model rats. The histopathological changes in myocardium were detected by hematoxylin & eosin (H&E) staining and Masson’s staining. Myocardium homogenate contents of collagen I and collagen III were evaluated by ELISA. The level of myocardial hydroxyproline (HYP) was determined by alkaline hydrolysis. Immunohistochemistry was used to examine collagen I. Western blotting was used to examine relevant proteins. As per the molecular docking study results, astragaloside IV may act on MyD88. Furthermore, astragaloside IV improved hemodynamic disorders, alleviated pathological changes, and reduced abnormal collagen deposition and myocardial HYP in vivo. Astragaloside IV significantly reduced the overexpression of TLR4, MyD88, NF‐Κb, and TGF‐β, which further validated the molecular docking findings. Hence, astragaloside IV ameliorates AMI by reducing inflammation and blocking TLR4/MyD88/NF‐κB signaling. These results indicate that astragaloside IV may alleviate AMI. Practical applications Astragaloside IV, a small active substance extracted from Astragalus membranaceus, has demonstrated potent protective effects against cardiovascular ischemia/reperfusion, diabetic nephropathy, and other diseases. Molecular docking experiments showed that astragaloside IV might act on the myeloid differentiation factor 88 (MyD88). Astragaloside IV can effectively reduce the overexpression of TLR4, MyD88, and NF‐κB p65, indicating that astragaloside IV inhibits inflammation via TLR4/MyD88/NF‐κB signaling pathway. These results indicate that astragaloside IV may alleviate acute myocardial infarction.

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Modified citrus pectin ameliorates myocardial fibrosis and inflammation via suppressing galectin-3 and TLR4/MyD88/NF-κB signaling pathway

Cited by 106 publications

References 53 publications

Extracellular CIRP Induces an Inflammatory Phenotype in Pulmonary Fibroblasts via TLR4

Extracellular CIRP Induces an Inflammatory Phenotype in Pulmonary Fibroblasts via TLR4

Latifolin protects against myocardial infarction by alleviating myocardial inflammatory via the HIF-1α/NF-κB/IL-6 pathway

Astragaloside IV prevents acute myocardial infarction by inhibiting the TLR4/MyD88/NF‐κB signaling pathway

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