circACTR2: A Novel Mechanism Regulating High Glucose-Induced Fibrosis in Renal Tubular Cells &lt;i&gt;via&lt;/i&gt; Pyroptosis

Su, Wen; Li, Shuangliang; Li, Lulu; Fan, Qiuling

doi:10.1248/bpb.b19-00901

Cited by 52 publications

(42 citation statements)

References 30 publications

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“…Knockout of circACTR2 significantly inhibited high-glucose–induced IL-1β release, and the production of collagen IV and fibronectin in HK-2 cells. By clarifying the role of circRNAs in the renal tubular cell pyroptosis-related inflammasome, new insights into the pathogenesis and treatment strategies of DKD may be attained ( 121 ). Li et al.…”

Section: Correlation Of the Pyroptosis-related Inflammasome Pathway Wmentioning

confidence: 99%

Relevance of the Pyroptosis-Related Inflammasome Pathway in the Pathogenesis of Diabetic Kidney Disease

2021

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Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD) in many developed and developing countries. Pyroptosis is a recently discovered form of programmed cell death (PCD). With progress in research on DKD, researchers have become increasingly interested in elucidating the role of pyroptosis in DKD pathogenesis. This review focuses on the three pathways of pyroptosis generation: the canonical inflammasome, non-canonical inflammasome, and caspase-3-mediated inflammasome pathways. The molecular and pathophysiological mechanisms of the pyroptosis-related inflammasome pathway in the development of DKD are summarized. Activation of the diabetes-mediated pyroptosis-related inflammasomes, such as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Toll-like receptor 4 (TLR4), caspase-1, interleukin (IL)-1β, and the IL-18 axis, plays an essential role in DKD lesions. By inhibiting activation of the TLR4 and NLRP3 inflammasomes, the production of caspase-1, IL-1β, and IL-18 is inhibited, thereby improving the pathological changes associated with DKD. Studies using high-glucose–induced cell models, high-fat diet/streptozotocin-induced DKD animal models, and human biopsies will help determine the spatial and temporal expression of DKD inflammatory components. Recent studies have confirmed the relationship between the pyroptosis-related inflammasome pathway and kidney disease. However, these studies are relatively superficial at present, and the mechanism needs further elucidation. Linking these findings with disease activity and prognosis would provide new ideas for DKD research.

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Section: Correlation Of the Pyroptosis-related Inflammasome Pathway Wmentioning

confidence: 99%

Relevance of the Pyroptosis-Related Inflammasome Pathway in the Pathogenesis of Diabetic Kidney Disease

2021

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“…Wen et al have reported that circACTR2 knockdown inhibits pyroptosis and reduces IL-1β secretion in HG-stimulated fibrosis in renal tubular cells. 183 The authors have detected a new circRNA, circACTR2, that modulates HG-stimulated fibrosis, inflammation, and pyroptosis in proximal tubular cells. Therefore, targeting the circRNAs can serve unique insight regulating pyroptosis into DN’s pathogenesis and create a novel therapeutic strategy in the future.…”

Section: Targeting Inflammasome and Pyroptosis For The Therapeutic Implications Of Diabetic Complicationsmentioning

confidence: 99%

Role of Pyroptosis in Diabetes and Its Therapeutic Implications

Mamun¹,

Wu²,

Nasrin³

et al. 2021

JIR

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Pyroptosis is mainly considered as a new pro-inflammatory mediatedprogrammed cell death. In addition, pyroptosis is described by gasdermin-induced pore formation on the membrane, cell swelling and rapid lysis, and several pro-inflammatory mediators interleukin-1β (IL-1β) and interleukin-18 (IL-18) release. Extensive studies have shown that pyroptosis is commonly involved by activating the caspase-1-dependent canonical pathway and caspase-4/5/11-dependent non-canonical pathway. However, pyroptosis facilitates local inflammation and inflammatory responses. Current researches have reported that pyroptosis promotes the progression of several diabetic complications. Emerging studies have suggested that some potential molecules targeting the pyroptosis and inflammasome signaling pathways could be a novel therapeutic avenue for managing and treating diabetes and its complications in the near future. Our narrative review concisely describes the possible mechanism of pyroptosis and its progressive understanding of the development of diabetic complications.

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“…Notably, with the research trends of epigenetics, the gene therapy of IL-22 and some types of long-non coding RNA (lncRNA) also perform great effects on inhibiting renal cell pyroptosis and, thus, attenuating kidney fibrosis and DKD progression [ 15 , 18 , 32 , 132 , 133 ].…”

Section: Therapeutic Drugs Targeting Pyroptosis For Dkd Treatmentmentioning

confidence: 99%

New Insights into the Mechanisms of Pyroptosis and Implications for Diabetic Kidney Disease

Lin

Cheng

et al. 2020

IJMS

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Pyroptosis is one special type of lytic programmed cell death, featured in cell swelling, rupture, secretion of cell contents and remarkable proinflammation effect. In the process of pyroptosis, danger signalling and cellular events are detected by inflammasome, activating caspases and cleaving Gasdermin D (GSDMD), along with the secretion of IL-18 and IL-1β. Pyroptosis can be divided into canonical pathway and non-canonical pathway, and NLRP3 inflammasome is the most important initiator. Diabetic kidney disease (DKD) is one of the most serious microvascular complications in diabetes. Current evidence reported the stimulatory role of hyperglycaemia-induced cellular stress in renal cell pyroptosis, and different signalling pathways have been shown to regulate pyroptosis initiation. Additionally, the inflammation and cellular injury caused by pyroptosis are tightly implicated in DKD progression, aggravating renal fibrosis, glomerular sclerosis and tubular injury. Some registered hypoglycaemia agents exert suppressive activity in pyroptosis regulation pathway. Latest studies also reported some potential approaches to target the pyroptosis pathway, which effectively inhibits renal cell pyroptosis and alleviates DKD in in vivo or in vitro models. Therefore, comprehensively compiling the information associated with pyroptosis regulation in DKD is the main aim of this review, and we try to provide new insights for researchers to dig out more potential therapies of DKD.

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circACTR2: A Novel Mechanism Regulating High Glucose-Induced Fibrosis in Renal Tubular Cells <i>via</i> Pyroptosis

Cited by 52 publications

References 30 publications

Relevance of the Pyroptosis-Related Inflammasome Pathway in the Pathogenesis of Diabetic Kidney Disease

Relevance of the Pyroptosis-Related Inflammasome Pathway in the Pathogenesis of Diabetic Kidney Disease

Role of Pyroptosis in Diabetes and Its Therapeutic Implications

New Insights into the Mechanisms of Pyroptosis and Implications for Diabetic Kidney Disease

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