Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Leukocytes and Plasma of Children with Nonalcoholic Fatty Liver Disease

Trojanek, Joanna; Michałkiewicz, Jacek; Grzywa-Czuba, Renata; Jańczyk, Wojciech; Gackowska, Lidia; Kubiszewska, Izabela; Helmin-Basa, Anna; Wierzbicka-Rucińska, Aldona; Szalecki, Mieczysław; Socha, Piotr

doi:10.1155/2020/8327945

Cited by 8 publications

(9 citation statements)

References 39 publications

(37 reference statements)

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“…This is in line with previous research demonstrating that HRW potently reduced smooth muscle cell migration by inhibiting MMP-9 and MMP-2 [ 27 ]. The serum expression of MMPs is correlated with the serum levels of markers of liver damage [ 28 ], which were not significantly altered in either group. This raises the possibility that the null effects of HRW on MMPs could be due to their lower expression in the NAFLD subjects compared to the studies in which MMPs were significantly upregulated by a greater stimulus [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Biological Effects of Hydrogen Water on Subjects with NAFLD: A Randomized, Placebo-Controlled Trial

et al. 2022

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Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant, tendency of increased levels of 8-hydroxy-2’-deoxyguanosine and malondialdehyde in the HRW group. This mild increase may be indicative of the hormetic effects of molecular hydrogen that occurred prior to the significant clinical improvements reported in previous longer-term studies. The favorable trends in this study in conjunction with previous animal and clinical findings suggest that HRW may serve as an important adjuvant therapy for promoting and maintaining optimal health and wellness. Longer term studies focused on prevention, maintenance, or treatment of NAFLD and early stages of NASH are warranted.

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Section: Discussionmentioning

confidence: 99%

Biological Effects of Hydrogen Water on Subjects with NAFLD: A Randomized, Placebo-Controlled Trial

et al. 2022

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“…the degradation of the extracellular matrix [36][37][38]. TIMPs could control the MMP activity, and MMP-2 could digest fibrillar collagen peptides and newly formed collagen fibers to degrade collagen [39,40].…”

Section: Discussionmentioning

confidence: 99%

Effects of Dendrobium Polysaccharides on the Functions of Human Skin Fibroblasts and Expression of Matrix Metalloproteinase-2 under High-Glucose Conditions

Cao

et al. 2021

International Journal of Endocrinology

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The effects of Dendrobium polysaccharides (PDC) on the functions of human skin fibroblasts (HSFs) and expression of matrix metalloproteinase-2 under high-glucose conditions and exploration of the underlying mechanism remain unclear. We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis and flow cytometry to evaluate the cell viability and apoptosis. The collagen levels were determined by the Sircol™ Collagen Assay. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase inhibitor (TIMP-2) mRNA. We found the following: (1) under the high-glucose condition, the HSF cell viability, the expression of TIMP-2 mRNA, and the collagen levels were reduced, while the apoptosis rate and the expression of MMP-2 mRNA increased ( P < 0.05 ). (2) In the high-glucose + PDC group, the PDC reversed the changes in the collagen level, viability, and apoptosis rate of the HSF cells caused by high glucose, with the expression of protein and TIMP-2 mRNA increased and the level of MMP-2 mRNA decreased ( P < 0.05 ). This is the first time attempting to reveal that PDC can exhibit protective effects on HSF under high-glucose conditions, which may be related to the upregulation of the TIMP-2 expression and inhibition of the MMP-2 expression.

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“…MMP9 performs a vital role in modulating and degrading gelatins, collagens, and other ECM compounds ( D’Amico et al, 2010 ; Lachowski et al, 2019 ). A decreased MMP9 level is associated with more advanced fibrosis and serum liver injury indexes (AST, GGT) in NAFLD patients, while increased MMP9 activity could precede the clearance of the fibrotic matrix ( Goyale et al, 2021 ; Trojanek et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Investigation of the potential mechanism of the Shugan Xiaozhi decoction for the treatment of nonalcoholic fatty liver disease based on network pharmacology, molecular docking and molecular dynamics simulation

Yang

Jiang

et al. 2022

PeerJ

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Background Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease, the incidence of which increases annually. Shugan Xiaozhi (SGXZ) decoction, a composite traditional Chinese medicinal prescription, has been demonstrated to exert a therapeutic effect on NAFLD. In this study, the potential bioactive ingredients and mechanism of SGXZ decoction against NAFLD were explored via network pharmacology, molecular docking, and molecular dynamics simulation. Methods Compounds in SGXZ decoction were identified and collected from the literature, and the corresponding targets were predicted through the Similarity Ensemble Approach database. Potential targets related to NAFLD were searched on DisGeNET and GeneCards databases. The compound–target–disease and protein-protein interaction (PPI) networks were constructed to recognize key compounds and targets. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed on the targets. Molecular docking was used to further screen the potent active compounds in SGXZ. Finally, molecular dynamics (MD) simulation was applied to verify and validate the binding between the most potent compound and targets. Results A total of 31 active compounds and 220 corresponding targets in SGXZ decoction were collected. Moreover, 1,544 targets of NAFLD were obtained, of which 78 targets intersected with the targets of SGXZ decoction. Key compounds and targets were recognized through the compound–target–disease and PPI network. Multiple biological pathways were annotated, including PI3K-Akt, MAPK, insulin resistance, HIF-1, and tryptophan metabolism. Molecular docking showed that gallic acid, chlorogenic acid and isochlorogenic acid A could combine with the key targets. Molecular dynamics simulations suggested that isochlorogenic acid A might potentially bind directly with RELA, IL-6, VEGFA, and MMP9 in the regulation of PI3K–Akt signaling pathway. Conclusion This study investigated the active substances and key targets of SGXZ decoction in the regulation of multiple-pathways based on network pharmacology and computational approaches, providing a theoretical basis for further pharmacological research into the potential mechanism of SGXZ in NAFLD.

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Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Leukocytes and Plasma of Children with Nonalcoholic Fatty Liver Disease

Cited by 8 publications

References 39 publications

Biological Effects of Hydrogen Water on Subjects with NAFLD: A Randomized, Placebo-Controlled Trial

Biological Effects of Hydrogen Water on Subjects with NAFLD: A Randomized, Placebo-Controlled Trial

Effects of Dendrobium Polysaccharides on the Functions of Human Skin Fibroblasts and Expression of Matrix Metalloproteinase-2 under High-Glucose Conditions

Investigation of the potential mechanism of the Shugan Xiaozhi decoction for the treatment of nonalcoholic fatty liver disease based on network pharmacology, molecular docking and molecular dynamics simulation

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