Sodium butyrate alleviates high-glucose-induced renal glomerular endothelial cells damage via inhibiting pyroptosis

Gu, Junjie; Huang, Wei; Zhang, Wenqian; Zhao, Tingting; Gao, Chenlin; Gan, Wen-Jun; Rao, Mingyue; Chen, Qing; Guo, Man; Xu, Yong; Xu, Youhua

doi:10.1016/j.intimp.2019.105832

Cited by 74 publications

(65 citation statements)

References 44 publications

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“…EthD-III, a type of cell membrane-impermeant nucleic acid dye, stains pyroptotic cells by entering through the membrane pores, but does not stain cells with intact membranes (Pan et al, 2018;Wang X. et al, 2019). The permeability of pyroptotic cell membranes can also be determined through the release of the cytoplasmic enzyme lactose dehydrogenase (LDH) (Ding et al, 2019;Gu et al, 2019). Recent studies showed that pyroptosis also occurs in cardiomyocytes (Pan et al, 2018;Meng et al, 2019;Wang X. et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Chemerin/CMKLR1 Axis Promotes Inflammation and Pyroptosis by Activating NLRP3 Inflammasome in Diabetic Cardiomyopathy Rat

et al. 2020

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Chemerin and its receptor CMKLR1 (a G-protein-coupled receptor) are inducers of inflammation, and play an important role in diabetic cardiomyopathy (DCM). In this study, we investigated the role of the chemerin/CMKLR1 axis in mediating inflammation and cell death in DCM. Sprague-Dawley rats, treated with a high-fat diet and low-dose of streptozotocin, were used as a DCM model. CMKLR1 expression was knocked down by siRNA (CMKLR1-siRNA) to evaluate the role of CMKLR1 in DCM. Chemerintreated H9c2 cells were used to investigate the factors acting downstream of the chemerin/CMKLR1 axis. LDH release and EthD-III staining were used to measure the ratio of cell death in vitro. CMKLR1-siRNA and siRNA against nucleotide-binding oligomerization domain-like receptors 3 (NLRP3-siRNA) were used to explore the mechanism underlying chemerin-induced inflammation and cell death. The results showed that the expression of chemerin, CMKLR1, NLRP3, pro-caspase-1, activated caspase-1, and mature IL-1β was increased in the DCM model rat. Myocardium of DCM model rats exhibited fibrosis, hypertrophy, a disorganized ultrastructure, and impaired function. Pyroptosis was observed in vivo and in vitro. Silencing of CMKLR1 in vivo attenuated the expression of NLRP3 and activated caspase-1 and IL-1β. CMKLR1-siRNA treatment attenuated cardiac inflammation, fibrosis, hypertrophy, and pyroptosis, and improved cardiac function in vivo. Silencing of either CMKLR1 or NLRP3 suppressed the levels of activated caspase-1, IL-1β, and pyroptosis; however, silencing of both CMKLR1 and NLRP3 further decreased the levels of mature IL-1β and pyroptosis. Overall, the results showed that the chemerin/CMKLR1 axis contributed to the development of DCM and that the NLRP3 inflammasome mediated the chemerin/CMLR1-induced inflammation and pyroptosis. These data indicate that silencing of the CMKLR1 gene might exert a protective effect against DCM.

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Section: Introductionmentioning

confidence: 99%

Chemerin/CMKLR1 Axis Promotes Inflammation and Pyroptosis by Activating NLRP3 Inflammasome in Diabetic Cardiomyopathy Rat

et al. 2020

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“…Supporting this prediction, recombinant GSDMD-NT shows robust and specific binding to phosphoinositides and cardiolipin [ 34 ]. In the progression of DKD, GSDMD-NT forms pores in the glomerular endothelial cells and gradually triggers cell death, which releases amounts of pro-inflammatory cytokines, such as IL-1β, and activates strong inflammation [ 35 ]. Meanwhile, tubular cell injury has something to do with the role of GSDMD-NT in promoting pyroptosis.…”

Section: Biology Of Pyroptosismentioning

confidence: 99%

“…Actually, the deterioration of renal function is closely associated with the intensity of pyroptosis regulation molecules. More recent studies showed renal resident cell pyroptosis strongly affects the renal function in DKD progression [ 35 , 42 , 98 , 99 ]. Furthermore, various activation signalling pathways of NLRP3 inflammasome contribute to the renal resident cell pyroptosis.…”

Section: Pathological Role Of Pyroptosis In Dkdmentioning

confidence: 99%

“…Thus, some researchers turned their focus to GSDMD and discovered that the release of IL-1β and IL-18 peaked at 24 h in the GECs with HG culture in vitro. Meanwhile, there was an experiment firstly revealing that HG induced GECs pyroptosis targeting GSDMD, and their experiment result demonstrated that silence of GSDMD inhibited GECs pyroptosis [ 35 ], indicating the participation of pyroptosis in GECs injury.…”

Section: Pathological Role Of Pyroptosis In Dkdmentioning

confidence: 99%

“…In fact, P2 receptor antagonists such as TNP-ATP and suramin both decreased the expression of pyroptosis related molecules and attenuated DKD, revealing a promising direction [ 89 ]. Additionally, short-chain fatty acid NaB is tested to prevent oxidative stress and relieve DKD by suppressing the pyroptosis canonical pathway [ 35 , 131 ].…”

Section: Therapeutic Drugs Targeting Pyroptosis For Dkd Treatmentmentioning

confidence: 99%

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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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Pyroptosis, metabolism, and tumor immune microenvironment

Gao

et al. 2021

Clinical & Translational Med

182

121

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In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger signals and pathogen infection. In manipulating the cleavage of gasdermins (GSDMs), researchers have found that GSDM proteins serve as the real executors and the deterministic players in fate decisions of pyroptotic cells. Whether inflammatory characteristics induced by pyroptosis could cause damage the host or improve immune activity is largely dependent on the context, timing, and response degree. Here, we systematically review current points involved in regulatory mechanisms and the multidimensional roles of pyroptosis in several metabolic diseases and the tumor microenvironment. Targeting pyroptosis may reveal potential therapeutic avenues.

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Sodium butyrate alleviates high-glucose-induced renal glomerular endothelial cells damage via inhibiting pyroptosis

Cited by 74 publications

References 44 publications

Chemerin/CMKLR1 Axis Promotes Inflammation and Pyroptosis by Activating NLRP3 Inflammasome in Diabetic Cardiomyopathy Rat

Chemerin/CMKLR1 Axis Promotes Inflammation and Pyroptosis by Activating NLRP3 Inflammasome in Diabetic Cardiomyopathy Rat

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

Pyroptosis, metabolism, and tumor immune microenvironment

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