Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy

Chen, Xiaowen; Peng, Sheng-Nan; Zeng, Huihong; Fu, Aixiang; Zhu, Qing

doi:10.4103/0253-7613.150319

Cited by 13 publications

(9 citation statements)

References 28 publications

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“…In an in vitro coculture system of IgA and mesangial cells, TLR4 mediates MAPK activation and MCP-1 secretion, indicating that TLR4 is engaged in glomerular mesangium damage by inducing inflammatory cytokines in IgAN [ 21 ]. TLR4 is also involved in the activation of NF-κB, triggering the transcription of mRNA encoding many inflammatory mediators, such as cytokines, chemokines, and fibrinogen and contributing significantly to the effects of the innate and adaptive immune responses [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis reveals novel hub gene pathways associated with IgA nephropathy

Xue

et al. 2020

Eur J Med Res

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Background Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy worldwide. However, the molecular events underlying IgAN remain to be fully elucidated. This study aimed to identify novel biomarkers of IgAN through bioinformatics analysis and elucidate the possible molecular mechanism. Methods Based on the microarray datasets GSE93798 and GSE37460 downloaded from the Gene Expression Omnibus database, the differentially expressed genes (DEGs) between IgAN samples and normal controls were identified. Using the DEGs, we further performed a series of functional enrichment analyses. Protein–protein interaction (PPI) networks of the DEGs were constructed using the STRING online search tool and were visualized using Cytoscape. Next, hub genes were identified and the most important module among the DEGs, Biological Networks Gene Ontology tool (BiNGO), was used to elucidate the molecular mechanism of IgAN. Results In total, 148 DEGs were identified, comprising 53 upregulated genes and 95 downregulated genes. Gene Ontology (GO) analysis indicated that the DEGs for IgAN were mainly enriched in extracellular exosome, region and space, fibroblast growth factor stimulus, inflammatory response, and innate immunity. Module analysis showed that genes in the top 1 significant module of the PPI network were mainly associated with innate immune response, integrin-mediated signaling pathway and inflammatory response. The top 10 hub genes were constructed in the PPI network, which could well distinguish the IgAN and control group in monocyte and tissue samples. We finally identified the integrin subunit beta 2 (ITGB2) and Fc fragment of IgE receptor Ig (FCER1G) genes that may play important roles in the development of IgAN. Conclusions We identified key genes along with the pathways that were most closely related to IgAN initiation and progression. Our results provide a more detailed molecular mechanism for the development of IgAN and novel candidate gene targets of IgAN.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis reveals novel hub gene pathways associated with IgA nephropathy

Xue

et al. 2020

Eur J Med Res

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“…[ 16 15 ] Binding with their ligands, TLRs initiate an intracellular signaling cascade, activate protein kinases, release cytokines, and enhance the expression of transcription factors[ 16 ] which results in the generation of mediators including adhesion molecules, chemokines, cytokines, and inflammatory responses. [ 42 ] The nuclear translocation of the NF-κB favored the hyperplasia of B-cell and therefore increased IgA synthesis. [ 43 ] TLRs have been conformed to be involved in the switch from IgM to IgA production in B-cells in experimental animals.…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy

Zou

Xiao

et al. 2017

Chinese Medical Journal

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Background:In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats.Methods:Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups: ControlTAK242, IgANTAK242, toll-like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4 inhibitor, TAK242) and ControlPio, IgANPio, Pio groups (rats were administrated with PPAR-γ agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR), serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin-1 beta (IL-1β) message ribonucleic acid (mRNA) and protein expression in renal tissues. Results were presented as mean ± standard deviation. Differences between groups were analyzed by one-way analysis of variance.Results:Compared to normal rats, experimental rats showed higher ACR (4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P < 0.05), obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-1β (48.28 ± 13.49 pg/ml vs. 35.56 ± 7.41pg/ml, P < 0.05), and renal expression of IL-1β and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-1β, and serum IL-1β were decreased in rats treated with TAK242, and the expression of TLR4 mRNA and protein was significantly reduced in Pio group compared to IgANPio group (1.22 ± 0.28 vs. 1.72 ± 0.45, P < 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P < 0.01).Conclusions:Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.

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“…Thus, a pronounced expression of (TLR4) in the renal tissue has been reported in rats with an experimentally created model of (IgA) nephropathy. At the same time, an improvement in biochemical parameters and a decrease in tubulointerstitial fibrosis were accompanied by a decrease in (TLR4) expression [4].…”

Section: The Role Of Natural Resistance Factors In the Pathogenesis Of (Gn)mentioning

confidence: 85%

Immunopathogenic mechanisms of primary glomerulonephritis

Karzakova

Zhuravleva

Abdelgafur

et al. 2021

Journal of Bioscience and Applied Research

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The low effectiveness of the existing ways of treatment of glomerulonephritis (GN) requires the development of new treatment methods and profound studying of mechanisms of development of (GN). A review of modern literature data indicates a relationship between the development of (GN) with infection and activation of various components of the immune response. Pathogen-associated molecular patterns of infectious pathogens act as "danger signals" that activate Toll-like receptors of innate immune cells, as a result, a cascade of intracellular chain reactions is triggered, causing the production of growth factors and cytokines. The cytokine environment determines the pathway of differentiation of (CD 4 + ) helper cells into (Th1), (Th2), (Th17), and regulatory T cells (T reg). According to published data, a key link in the (GN) immunopathogenesis is an imbalance in the ratio of the activity of subpopulations of T helper cells, manifesting inhibition activity of (T reg) on a background of activation of effector cells ( T eff ) -( Th1), (Th2), (Th17). The activity of (Th1), (Th17)-cells are realized in the cellular mechanisms of the immunopathogenesis of (GN), while (Th2)-cells provide activation of the humoral component of adaptive immunity and the production of antibodies involved in the formation of immune complexes (ICs). This is a general scheme of the immunopathogenesis of (GN), which has specific variations depending on the clinical and morphological form of (GN). In post-infectious (GN), the activation of the humoral link of adaptive immunity with the formation of (ICs) and their subsequent deposition in the capillaries of the glomeruli comes to the fore. A feature of the immune complex process in patients with (IgA) nephropathy is the formation of "nephritogenic" ICs containing abnormal (IgA) (with impaired glycosylation of the IgA molecule) and anti-

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Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy

Cited by 13 publications

References 28 publications

Bioinformatics analysis reveals novel hub gene pathways associated with IgA nephropathy

Bioinformatics analysis reveals novel hub gene pathways associated with IgA nephropathy

Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy

Immunopathogenic mechanisms of primary glomerulonephritis

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