TNFα enhances TLR3‐dependent effects on MMP‐9 expression in human mesangial cells

Merkle, Monika; Ribeiro, Andrea; Köppel, Simone; Wörnle, Markus

doi:10.1042/cbi20120282

Cited by 8 publications

(5 citation statements)

References 24 publications

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“…It has been indicated that MMPs, particularly MMP-2 and MMP-9, have a key role in podocyte injury (22). Previous studies have also demonstrated that ADR-induced inhibition of podocyte migration and cell injury may be associated with the downregulation of MMP-2 and MMP-9 at the mRNA and protein level (22,23), which was consistent with the results of the present study. Furthermore, the present study indicated that AST increased the expression of MMP-2 and MMP-9 compared with that in the podocyte injury group.…”

Section: Discussionsupporting

confidence: 82%

Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury

et al. 2018

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Abstract. Nephrotic syndrome (NS) is the most common kidney disease in clinical practice and may lead to end-stage renal failure. Astragalosides (AST) have been clinically tested for the treatment of NS, but their mechanism of action has remained to be elucidated. The aim of the present study was to investigate the effect of AST on the structure and function of podocytes with adriamycin (ADR)-induced damage and to elucidate the underlying molecular mechanisms. The mouse podocyte clone 5 (MPC5) immortalized mouse podocyte cell line was treated with 0.5 µmol/l ADR to establish a podocyte injury model. The MPC5 podocytes were divided into a control group, a podocyte injury group and a low-, medium-and high-concentration AST treatment group. The results indicated that the survival rate of the podocyte injury group was significantly decreased compared with that in the control group and each AST-treated group had an increased survival rate compared with that in the podocyte injury group. Furthermore, each dose of AST significantly inhibited the ADR-associated increases the levels of lactate dehydrogenase and malondialdehyde and the decrease in the activity of superoxide dismutase in MPC5 podocytes. In addition, AST improved the migration ability of MPC5 podocytes and suppressed the cytoskeletal rearrangement associated with ADR-induced damage. Furthermore, matrix metalloproteinase (MMP)-2 and -9 were decreased in the podocyte injury group, which was inhibited by different concentrations of AST. Thus, AST was able to maintain the balance of oxidative stress in podocytes cultured with ADR and protect them from ADR-induced injury. The mechanism may be associated with the upregulation of MMPs.

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Section: Discussionsupporting

confidence: 82%

Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury

et al. 2018

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“…One possible mechanism of TLR3 involved in the pathogenesis of CKD including lupus nephritis and chronic inflammatory renal disease may be due to its role in triggering the glomerular mesangial cells to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury [39][40][41][42] .…”

Section: Discussionmentioning

confidence: 99%

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

He¹,

Peng²,

Wang³

et al. 2015

Am J Nephrol

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Background: Immunoglobulin class-switch recombination (CSR) is crucial for the expression of IgA, and it plays a vital role in the physiopathology of IgA nephropathy (IgAN). The aim of the study is to investigate the effect of polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat model. Methods: Blood samples and tonsillar tissue specimens were obtained from 24 patients with IgAN and 26 patients with chronic tonsillitis as control. We also used the IgAN rat model to investigate the relationship between viral infection and IgA CSR. Results: Immunohistochemical and ELISA western blotting examination revealed that the TLR3/BAFF axis is activated in IgAN patients when compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With 200 μg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis and IgA CSR in vivo. Conclusion: These data points toward the role of TLR3/BAFF axis in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with virus infection results in impaired mucosal and systemic IgA responses.

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“…[37] Many studies have shown that MMP9 promotes inflammatory cell aggregation and infiltration, and its high expression in connective tissue diseases often causes joint destruction by degrading the extracellular matrix of the cartilage and bone. [38] Chen et al showed that TGFB1 is highly expressed in the remission phase of GA and contributes to the growth and differentiation of fibroblasts for tissue repair. [39] SIRT1 is significantly deacetylated and involved in physiological processes, including cell cycle regulation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and molecular docking to explore the treatment potential and molecular mechanism of Si-Miao decoction against gouty arthritis

Ma,

Zeng,

Feng

et al. 2024

Medicine

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Gouty arthritis (GA) is a common metabolic rheumatological disease. Si-Miao decoction has therapeutic effects on GA. In our study, we investigated the mechanism of Si-Miao decoction against GA using network pharmacology and molecular docking analytical methods. The Traditional Chinese Medicine Systems Pharmacology Database was used as the basis for screening the main targets and agents of the Si-Miao decoction, and the Genecards, OMIM, and Drugbank databases were used to screen GA-related targets. They were analyzed using Venn with the drug targets to obtain the intersection targets. We used Cytoscape 3.9.1 to draw the “Drugs-Compounds-Targets” network and the String database for creative protein-protein interaction networks of target genes and filtered core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze the core targets. Molecular docking was performed using AutoDockTools to predict the binding capacity between nuclear targets and active components in the Si-Miao decoction. A total of 50 chemically active components containing 53 common targets of Si-Miao decoction anti-GA and 53 potential drug target proteins were identified. Core targets, namely, TNF, STAT3, SRC, PPARG, TLR4, PTGS2, MMP9, RELA, TGFB1, and SIRT1, were obtained through PPI network analysis. GO and KEGG analyses showed that the mechanism of anti-GA in Si-Miao decoction may proceed by regulating biological processes such as inflammatory factor levels, cell proliferation, apoptosis, and lipid and glucose metabolism, and modulating the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, NF-kappa B signaling pathway, and Toll-like receptor signaling pathway. We further screened the core targets, including PTGS2, MMP9, and PPAGR, as receptor proteins based on their degree value and molecular docking with the main active compounds in Si-Miao decoction, and found that baicalein had high affinity. In conclusion, Si-Miao decoction, through anti-inflammatory, apoptosis-regulating, and anti-oxidative stress action mechanisms in the treatment of GA.

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TNFα enhances TLR3‐dependent effects on MMP‐9 expression in human mesangial cells

Cited by 8 publications

References 24 publications

Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury

Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

Network pharmacology and molecular docking to explore the treatment potential and molecular mechanism of Si-Miao decoction against gouty arthritis

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