NF-kB Expression in IgA Nephropathy Outcome

Renal reactive oxygen species (ROS) and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation) of IgA nephropathy (IgAN), which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L.) Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB) activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN) model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1) reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2) inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3) decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4) inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5) inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder.

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“…Activation of the NF-κB pathway has been implicated in the acceleration and progression of IgAN [16], [31]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 96%

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

et al. 2013

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“…We determined the positive effects of infliximab administration on tubular structure, being enhanced dose-dependently. In a previous study, the expressions of NF-kB were shown to increase due to nephropathy (Silva et al, 2011). In another study, NF-kB was shown to be excessively activated in renal tubular cells following tubular damage (Nguyen et al, 2014).…”

Section: Page 12 Of 34mentioning

confidence: 91%

Tnf-α inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy

Sarıtemur

Çadırcı

et al. 2015

Environmental Toxicology and Pharmacology

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“…The NF-κB/TLR4 pathway is well-known for regulating immunological response [19]. Evidence has indicated that the NF-κB/TLR4 pathway activity is markedly increased in IgAN patients, and that the level of the NF-κB/TLR4 pathway is associated with poorer outcomes of IgAN patients [20,21]. As an immunosuppressant, TAC downregulates the NF-κB/TLR4 pathway in a protection effect in transplantation and IgAN patients [22–24].…”

Section: Discussionmentioning

confidence: 99%

Effect of Vitamin D and Tacrolimus Combination Therapy on IgA Nephropathy

et al. 2017

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BackgroundTo explore the effects and the mechanism of vitamin D (VD) and tacrolimus (TAC) combinatorial therapy in the treatment of IgA nephropathy (IgAN) in a rat model.Material/MethodsIgAN rat models constructed by oral immunization with bovine serum albumin (BSA) and lipopolysaccharide (LPS) (n=30) and were treated with: saline (model group), TAC (TAC group), or TAC+VD therapy (TAC+VD group) through gavage daily for 14 days. Serum creatinine (Scr), albumin (ALB), blood urea nitrogen (BUN), and urinary protein (UAE) levels were determined. Histopathology of renal tissues was examined after hematoxylin and eosin (H&E) staining. The levels of cytokines TGF-β1, IL-5, IFN-γ, and IL-4 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Changes in TLR4/NF-κB pathway were evaluated by western blot.ResultsBoth TAC and TAC+VD treatment significantly restored the dysregulated Scr, ALB, BUN, and UAE levels in IgAN rats. TAC+VD therapy more prominently restored Scr and UAE levels (p<0.05). TAC+VD therapy demonstrated superior efficacy in reducing glomerular mesangial cells hyperplasia, reducing thickening of the glomerular basement membrane and glomerular infiltration of inflammatory cells. Thymus and spleen indexes were also increased (p<0.05). The levels of TGF-β1, IL-5, and IL-4 of the TAC+VD group were also lower than those of the TAC group (p<0.05). The TAC+VD group also demonstrated increased IFN-γ, and decreased p-P65/P65 and TLR4 compared to the TAC group.ConclusionsTAC+VD combinatorial therapy can effectively alleviate renal tissue damage in IgAN rats by regulating immune response and the NF-κB/TLR4 pathway.

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NF-kB Expression in IgA Nephropathy Outcome

Cited by 21 publications

References 20 publications

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

Tnf-α inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy

Effect of Vitamin D and Tacrolimus Combination Therapy on IgA Nephropathy

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