Inflammasome activation in podocytes: a new mechanism of glomerular diseases

Xiong, Wei; Meng, Xianhong; Zhang, Chun

doi:10.1007/s00011-020-01354-w

Cited by 37 publications

(27 citation statements)

References 85 publications

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“…21 Recently, the NLRP3 inflammasome pathway, which is recognized as key pathophysiology of DN, has greatly caught the public's attention. 22,23 The NLRP3 inflammasome serves as an intracellular inflammatory machinery, which can be activated by HG condition. 24 Due to the lack of caspase recruitment domain, NLRP3 needs to be combined with ASC to recruit pro caspase1 and cut into mature caspase1 to participate in the release of inflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

<p>Mogroside IIIE Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Podocytes by the Activation of AMPK/SIRT1 Signaling Pathway</p>

Xue¹,

Mao²,

Chen³

et al. 2020

DMSO

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Background: Diabetic nephropathy (DN) is the leading cause of impaired renal function. The purpose of this study was to investigate the effects of Mogroside IIIE (MG IIIE), a cucurbitane-type compound isolated from Siraitia grosvenorii, in high glucose (HG)induced podocytes and the possible mechanisms. Methods: MPC-5 cells were cultured under normal glucose or HG conditions. After treatment with MG IIIE, cell viability was examined using a cell counting kit-8 assay. The contents of inflammatory factors and oxidative stress-related markers were determined using the corresponding kits. Additionally, apoptosis of MPC-5 cells was determined using flow cytometry assay and the levels of apoptosis-associated proteins were evaluated by Western blot analysis. Moreover, the expression of proteins in AMPK/SIRT1 signaling was tested and the compound C, an AMPK inhibitor, was used to study whether the effects of MG IIIE on HG-induced MPC-5 cells were mediated by activation of the AMPK/SIRT1 signaling pathway. Results: MG IIIE elevated the cell viability of HG-induced MPC-5 cells, reduced the concentrations of inflammatory cytokines and decreased the levels of oxidative stressrelated markers. What's more, the apoptosis of podocytes induced by HG was inhibited after MG IIIE intervention, accompanied by the upregulated expression of Bcl-2 and downregulated expression of Bax, cleaved caspase-3 and cleaved caspase-9. It was also found that MG IIIE could activate the AMPK/SIRT1 signaling, but compound C inhibited this pathway and reversed the inhibitory effects of MG IIIE on inflammation, oxidative stress and apoptosis in HG-stimulated podocytes. Conclusion: MG IIIE can alleviate HG-induced inflammation and oxidative stress of podocytes by the activation of AMPK-SIRT1 signaling.

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Section: Discussionmentioning

confidence: 99%

<p>Mogroside IIIE Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Podocytes by the Activation of AMPK/SIRT1 Signaling Pathway</p>

Xue¹,

Mao²,

Chen³

et al. 2020

DMSO

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“…Furthermore, recently, a strict involvement of NLR family pyrin domain containing 3 (NLRP3) Inflammasome in several pathophysiological processes has been described, which leads to podocyte injury and plays a central role in albuminuria [39].…”

Section: Glomerular Mechanisms Of Albuminuriamentioning

confidence: 99%

Role of Albuminuria in Detecting Cardio-Renal Risk and Outcome in Diabetic Subjects

et al. 2021

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The clinical significance of albuminuria in diabetic subjects and the impact of its reduction on the main cardiorenal outcomes by different drug classes are among the most interesting research focuses of recent years. Although nephrologists and cardiologists have been paying attention to the study of proteinuria for years, currently among diabetics, increased urine albumin excretion ascertains the highest cardio-renal risk. In fact, diabetes is a condition by itself associated with a high-risk of both micro/macrovascular complications. Moreover, proteinuria reduction in diabetic subjects by several treatments lowers both renal and cardiovascular disease progression. The 2019 joint ESC-EASD guidelines on diabetes, prediabetes and cardiovascular (CV) disease assign to proteinuria a crucial role in defining CV risk level in the diabetic patient. In fact, proteinuria by itself allows the diabetic patient to be staged at very high CV risk, thus affecting the choice of anti-hyperglycemic drug class. The purpose of this review is to present a clear update on the role of albuminuria as a cardio-renal risk marker, starting from pathophysiological mechanisms in support of this role. Besides this, we will show the prognostic value in observational studies, as well as randomized clinical trials (RCTs) demonstrating the potential improvement of cardio-renal outcomes in diabetic patients by reducing proteinuria.

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“…Moreover, MSU crystals promote macrophages to secrete transforming growth factor beta-1 (TGF-β1) through mediation of the metastatic tumor antigen 1/transglutaminase 2 (MTA1/TG2) signaling pathway [32] . TGF-β1 is a strong profibrotic cytokine, and aberrant TGF-β1 derived from MSU crystalinduced macrophages, together with above mechanisms, may promote renal fibrosis, as evidenced in in vitro [33][34][35] and in vivo [36,37] studies. It has been demonstrated that these extensive biological activities can promote inflammation and dysfunctions in cell metabolism, contributing to the loss of integrity of the glomerular filtration barrier, as outlined in Figure 2.…”

Section: Inflammasomementioning

confidence: 99%

The role of uric acid in renal damage - A history of inflammatory pathways and vascular remodeling

Russo¹,

Verzola²,

Cappadona³

et al. 2021

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The association of hyperuricemia with cardiovascular risk, hypertension, atherosclerosis, metabolic syndrome, mortality, and chronic kidney disease has been largely described in clinical studies. Several pathogenetic mechanisms explaining uric acid mediated renal damage have been hypothesized, including crystal deposition, oxidative stress, arteriolosclerosis, and glomerular hypertension. Currently, two explanations for hyperuricemiainduced renal injury are the most widely accepted. Firstly, the fact that uric acid is recognized by receptors involved in the innate immune response as a dangerous molecule appears to be a powerful trigger for the inflammatory cascade, which ultimately lead to renal fibrosis. Secondly, serum uric acid has been demonstrated to be implicated in the renin-angiotensin system activation and nitric oxide synthesis inhibition, which promote endothelial dysfunction and proliferation of vascular smooth muscle cells, resulting in glomerulosclerosis and interstitial fibrosis. In this review, we focus on experimental data demonstrating pathophysiological mechanisms linking uric acid to inflammation and oxidative stress, which contribute to the development and progression of renal injury. In addition, we describe endothelial and vascular dysfunction crucial playmakers in kidney impairment induced by uric acid.

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Inflammasome activation in podocytes: a new mechanism of glomerular diseases

Cited by 37 publications

References 85 publications

<p>Mogroside IIIE Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Podocytes by the Activation of AMPK/SIRT1 Signaling Pathway</p>

<p>Mogroside IIIE Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Podocytes by the Activation of AMPK/SIRT1 Signaling Pathway</p>

Role of Albuminuria in Detecting Cardio-Renal Risk and Outcome in Diabetic Subjects

The role of uric acid in renal damage - A history of inflammatory pathways and vascular remodeling

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