NLRP3 deficiency ameliorates renal inflammation and fibrosis in diabetic mice

Wu, Ming; Han, Weiping; Song, Shan; Du, Yong; Liu, Chao; Chen, Nan; Wu, Haijiang; Shi, Yonghong; Duan, Huijun

doi:10.1016/j.mce.2018.08.002

Cited by 144 publications

(118 citation statements)

References 42 publications

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“…Considerable evidence has revealed a strong association between renal function and NLRP3. The NLRP3 knockout can attenuate renal dysfunction in a unilateral ureteral obstruction (UUO) model of CKD, improve renal function, and alleviate inflammation and the level of CTGF (TGF-β1 and connective tissue growth factor) in STZ-induced diabetic mice (Guo et al, 2017;Wu et al, 2018). The use of a specific inhibitor of the NLRP3 inflammasome 773 can prevent kidney dysfunction in a murine model of crystal nephropathy (Ludwig-Portugall et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Zhang

Fan

Cai

et al. 2020

Front. Cell Dev. Biol.

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163

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Fibrosis is a common phenotype that often leads to the progression of blood pressure-induced chronic kidney disease (CKD). TGF-beta plays an important role in promoting pathogenesis, and NLRP3 is a critical mediator in the progression of blood pressure-induced CKD. However, the pathophysiological roles of the TGF-betamediated NLRP3 pathway in modulating fibrosis in blood pressure-induced CKD have not been elucidated. The present study aims to investigate the contribution of TGFbeta-mediated NLRP3 inflammasome to renal fibrosis in rats with high blood pressure. By treating rats with angiotensin II (Ang II) for 14 days, we observed the development of fibrosis, characterized by epithelial-mesenchymal transition (EMT) markers [alphasmooth muscle actin (alpha-SMA), MMP-2, and MMP-9]. Immunohistochemical analysis further revealed that TGF-beta and NLRP3 inflammasome activation [high-mobility group box 1 (HMGB1), IL-1beta, and NLRP3] were significantly upregulated in the kidney of rats with Ang II-induced hypertension. Interestingly, we observed that Ang II could not increase the production of NLRP3 proteins, but TGF-beta could induce NLRP3 protein expression in cultured NRK-52E cells. Furthermore, we speculated that TGF-beta played a pathogenic role in Ang II-induced CKD because TGF-beta induced the activation of NLRP3 inflammasomes and Gasdermin D cleavage expression. We also proved that the pharmacological inhibition of NLRP3 by ISO caused a decrease in TGF-beta-induced NLRP3 inflammasome activation and the expression of EMT markers (alpha-SMA and CollagenI) and Gasdermin D cleavage. Collectively, these results suggest that TGF-beta-mediated NLRP3 inflammasome activation may cause the release of HMGB1 and an increase in Gasdermin D cleavage in NRK-52E, thereby contributing to renal fibrosis in Ang II-induced CKD. These findings provide novel insights into the pathogenic role of NLRP3 in CKD associated with high blood pressure.

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Section: Introductionmentioning

confidence: 99%

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Zhang

Fan

Cai

et al. 2020

Front. Cell Dev. Biol.

Self Cite

163

130

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“…Additionally, the NLRP3 inflammasome mediates the maturation and release of proinflammatory cytokines to initiate excessive inflammatory reactions, which cause irreversible damage to the body (Kanneganti et al, 2007). A large number of studies have also shown that the NLRP3 inflammasome is involved in the development of chronic kidney diseases (CKD) (Wu et al, 2018;Li et al, 2019;Mulay, 2019). Therefore, the role and regulation of the NLRP3 inflammasome during renal fibrosis are here reviewed.…”

Section: Introductionmentioning

confidence: 99%

Effect and Regulation of the NLRP3 Inflammasome During Renal Fibrosis

Zhang¹,

Wang²

2020

Front. Cell Dev. Biol.

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Renal fibrosis is a common pathological process where certain primary or secondary kidney diseases can continue to progress to the end-stage of the kidney disease; however, the molecular mechanisms underlying renal fibrosis remain unclear. Recently, research focusing on examining the function of inflammasomes has attracted a great deal of attention, and data derived from these research projects have increased our understanding of the effects and regulation of inflammasomes during renal fibrosis. Based on this, the present review summarizes recent findings in regard to NLRP3 inflammasome functions during various kidney diseases, and these findings indicate that the NLRP3 inflammasome not only mediates the inflammatory response but is also associated with pyroptosis, mitochondrial regulation, and myofibroblast differentiation during renal fibrosis. These novel findings provide us with a more in-depth understanding of the pathogenesis of renal fibrosis and will aid in the identification of new targets that can be used for the prevention and treatment of this disease.

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“…IL-1β increases the expression of IL-6 and IL-8 in primary human renal fibroblasts and mesangial cells [89][90][91]. IL-1β induces ROS production and fibrotic factor expression, such as that of TGF-β, collagen I, and fibronectin in tubular epithelial cells [85,92,93]. Additionally, IL-1β promotes tubular epithelial cells to transdifferentiate into fibroblast-like phenotype, which is critical in the progression of renal fibrosis [94,95].…”

Section: Il-1βmentioning

confidence: 99%

“…NLRP3 inflammasome can be activated by glucose in glomerular endothelial cells and podocytes [96]. A few in vivo studies have shown that NLRP3 deficiency reduces renal inflammation, ECM accumulation, and fibrosis [86,92,[103][104][105]. In addition to IL-1β, NLRP3 inflammasome can also trigger IL-18 maturation, which is associated with the pathogenesis of various kidney diseases [105][106][107][108].…”

Section: Il-1βmentioning

confidence: 99%

IL-20 in Acute Kidney Injury: Role in Pathogenesis and Potential as a Therapeutic Target

Lin

Hsu

2020

IJMS

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Acute kidney injury (AKI) causes over 1 million deaths worldwide every year. AKI is now recognized as a major risk factor in the development and progression of chronic kidney disease (CKD). Diabetes is the main cause of CKD as well. Renal fibrosis and inflammation are hallmarks in kidney diseases. Various cytokines contribute to the progression of renal diseases; thus, many drugs that specifically block cytokine function are designed for disease amelioration. Numerous studies showed IL-20 functions as a pro-inflammatory mediator to regulate cytokine expression in several inflammation-mediated diseases. In this review, we will outline the effects of pro-inflammatory cytokines in the pathogenesis of AKI and CKD. We also discuss the role of IL-20 in kidney diseases and provide a potential therapeutic approach of IL-20 blockade for treating renal diseases.

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NLRP3 deficiency ameliorates renal inflammation and fibrosis in diabetic mice

Cited by 144 publications

References 42 publications

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Effect and Regulation of the NLRP3 Inflammasome During Renal Fibrosis

IL-20 in Acute Kidney Injury: Role in Pathogenesis and Potential as a Therapeutic Target

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