Upregulation of matrix metalloproteinase 9 (MMP9)/tissue inhibitor of metalloproteinase 1 (TIMP1) and MMP2/TIMP2 ratios may be involved in lipopolysaccharide-induced acute lung injury

Chen, Guobing; Ge, Dongyu; Zhu, Bizhen; Shi, Huixuan; Ma, Qi

doi:10.1177/0300060520919592

Cited by 27 publications

(24 citation statements)

References 37 publications

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“…MMP-9 also has a cleavage effect on the ligand, CL8, that promotes the chemotaxis of neutrophils ( 37 ). In addition, MMP-9 acts as a gelatinase to hydrolyze the basement membrane and extracellular matrix of the blood vessels, directly impacting the structure of the respiratory tract and lungs ( 12 , 38 ). Thus, MMP-9 activity was also measured in the current study.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression

et al. 2021

Front. Immunol.

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Endotoxin-induced lung injury is one of the major causes of death induced by endotoxemia, however, few effective therapeutic options exist. Hydrogen inhalation has recently been shown to be an effective treatment for inflammatory lung injury, but the underlying mechanism is unknown. In the current study we aim to investigate how hydrogen attenuates endotoxin-induced lung injury and provide reference values for the clinical application of hydrogen. LPS was used to establish an endotoxin-induced lung injury mouse model. The survival rate and pulmonary pathologic changes were evaluated. THP-1 and HUVECC cells were cultured in vitro. The thioredoxin 1 (Trx1) inhibitor was used to evaluate the anti-inflammatory effects of hydrogen. Hydrogen significantly improved the survival rate of mice, reduced pulmonary edema and hemorrhage, infiltration of neutrophils, and IL-6 secretion. Inhalation of hydrogen decreased tissue factor (TF) expression and MMP-9 activity, while Trx1 expression was increased in the lungs and serum of endotoxemia mice. LPS-stimulated THP-1 and HUVEC-C cells in vitro and showed that hydrogen decreases TF expression and MMP-9 activity, which were abolished by the Trx1 inhibitor, PX12. Hydrogen attenuates endotoxin-induced lung injury by decreasing TF expression and MMP-9 activity via activating Trx1. Targeting Trx1 by hydrogen may be a potential treatment for endotoxin-induced lung injury.

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Section: Discussionmentioning

confidence: 99%

Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression

et al. 2021

Front. Immunol.

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“…Additionally, HCC derived IL1A and TGFA appear to be promoting upregulation of TME-derived MMP9 and MMP2 , respectively. TIMP2 and TIMP1 are specific inhibitors of MMP2 and MMP9 , respectively ( Chen et al, 2020 ). MMP2 degrades ECM components of the basement membrane and facilitates tumor invasion while TIMP2 regulates MMP2 activity.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Porcine HCC Xenografts Provides Insights Into Tumor Cell Microenvironment Signaling

et al. 2021

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, representing the most common form of liver cancer. As HCC incidence and mortality continue to increase, there is a growing need for improved translational animal models to bridge the gap between basic HCC research and clinical practice to improve early detection and treatment strategies for this deadly disease. Recently the Oncopig cancer model—a novel transgenic swine model that recapitulates human cancer through Cre recombinase induced expression of KRASG12D and TP53R167H driver mutations—has been validated as a large animal translational model for human HCC. Due to the similar size, anatomy, physiology, immunology, genetics, and epigenetics between pigs and humans, the Oncopig has the potential to improve translation of novel diagnostic and therapeutic modalities into clinical practice. Recent studies have demonstrated the importance of tumor cells in shaping its surrounding microenvironment into one that is more proliferative, invasive, and metastatic; however, little is known about the impact of microenvironment signaling on HCC tumor biology and differential gene expression between HCC tumors and its tumor microenvironment (TME). In this study, transcriptional profiling was performed on Oncopig HCC xenograft tumors (n = 3) produced via subcutaneous injection of Oncopig HCC cells into severe combined immunodeficiency (SCID) mice. To differentiate between gene expression in the tumor and surrounding tumor microenvironment, RNA-seq reads originating from porcine (HCC tumor) and murine (microenvironment) cells were bioinformatically separated using Xenome. Principle component analysis (PCA) demonstrated clustering by group based on the expression of orthologous genes. Genes contributing to each principal component were extracted and subjected to functional analysis to identify alterations in pathway signaling between HCC cells and the microenvironment. Altered expression of genes associated with hepatic fibrosis deposition, immune response, and neo angiogenesis were observed. The results of this study provide insights into the interplay between HCC and microenvironment signaling in vivo, improving our understanding of the interplay between HCC tumor cells, the surrounding tumor microenvironment, and the impact on HCC development and progression.

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“…e ECM is the main structural component of the alveolar-capillary membrane, which not only plays a mechanical-supporting and mechanical-connecting role between cells but is also important in maintaining normal Evidence-Based Complementary and Alternative Medicine tissue structure and function [9,32,33]. Previous work has shown that ECM metabolic disorders are involved in the pathophysiological process of ALI and chronic lung injury [34,35]. MMPs are proteolytic enzymes that rely on the metal ions zinc and calcium and use ECM components as hydrolysis substrates; they play an important role in maintaining the normal transformation of ECM, tissue damage and repair, inflammatory response, and other pathophysiological processes [11,12,36].…”

Section: Discussionmentioning

confidence: 99%

“…The ECM is the main structural component of the alveolar-capillary membrane, which not only plays a mechanical-supporting and mechanical-connecting role between cells but is also important in maintaining normal tissue structure and function [ 9 , 32 , 33 ]. Previous work has shown that ECM metabolic disorders are involved in the pathophysiological process of ALI and chronic lung injury [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Salvia miltiorrhiza Injection Alleviates LPS‐Induced Acute Lung Injury by Adjusting the Balance of MMPs/TIMPs Ratio

Chen

Zhu

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Salvia miltiorrhiza injection (SMI) is a classical traditional Chinese medicine, which plays an active role in the treatment of many diseases such as promoting blood circulation, removing blood stasis, reducing inflammatory reaction, and improving acute lung injury (ALI). Previous studies have shown that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the pathophysiological process of ALI. However, the relationship between SMI and MMPs/TIMPs remains unclear. In this study, Wistar rats were randomly divided into control group (NC), Salvia miltiorrhiza group (SM), lipopolysaccharide group (LPS), and Salvia miltiorrhiza treatment group (Tsm). The four groups were subdivided into four time points (2, 6, 12, and 24 hours), and specimens were collected after animal sacrifice at each time point. Serum TNF-α and IL-6 levels were detected by ELISA. The degree of lung injury was determined by lung tissue hematoxylin-eosin staining, lung wet/dry weight (W/D) ratio, and lung permeability index. The changes in lung MMPs/TIMPs protein and mRNA were detected by Western blot and real-time quantitative PCR. The results showed that rats injected with LPS experience acute lung injury, and the ratio of MMPs/TIMPs in lung tissues increased gradually with time. In the Tsm group, the ratio of MMPs/TIMPs decreased gradually, and likewise, the balance was gradually restored, while indicators related to lung injury were gradually declined. These data suggest that SMI alleviates LPS-induced acute lung injury; this protective effect may be related to regulation of the balance of MMPs/TIMPs ratio.

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Upregulation of matrix metalloproteinase 9 (MMP9)/tissue inhibitor of metalloproteinase 1 (TIMP1) and MMP2/TIMP2 ratios may be involved in lipopolysaccharide-induced acute lung injury

Cited by 27 publications

References 37 publications

Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression

Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression

Transcriptional Profiling of Porcine HCC Xenografts Provides Insights Into Tumor Cell Microenvironment Signaling

Salvia miltiorrhiza Injection Alleviates LPS‐Induced Acute Lung Injury by Adjusting the Balance of MMPs/TIMPs Ratio

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