Apocynin inhibited NLRP3/XIAP signalling to alleviate renal fibrotic injury in rat diabetic nephropathy

Xin, Rui; Sun, Xiao‐Feng; Wang, Ziying; Yuan, Wendan; Jiang, Wei; Wang, Lin; Xiang, Yuzhi; Zhang, Hongqin; Li, Xiaoyan; Hou, Yun; Sun, Wangnan; Du, Pengchao

doi:10.1016/j.biopha.2018.07.036

Cited by 38 publications

(25 citation statements)

References 49 publications

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“…NLRP3 inflammasome is the most studied inflammasome and has been proposed to be a potential therapeutic target for the treatment of DN supported by increasing evidence [40, 41]. Several studies have also shown promising results for DN treatment by targeting NLRP3 [42-44]. NLRP3, along with the adaptor protein apoptosis-associated spec-like protein containing a CARD (ASC), activates caspase-1 through inflammasome assembly and mediates the change of IL-1β from an inactive precursor to the secreted active form and the process of pyroptosis [45].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c/NLRP3 Axis

Zhan¹,

Huang²,

Huang³

et al. 2020

Kidney Blood Press Res

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Introduction: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and is considered to be a sterile inflammatory disease. Increasing evidence suggest that pyroptosis and subsequent inflammatory response play a key role in the pathogenesis of DN. However, the underlying cellular and molecular mechanisms responsible for pyroptosis in DN are largely unknown. Methods: The rat models of DN were successfully established by single 65 mg/kg streptozotocin treatment. Glomerular mesangial cells were exposed to 30 mmol/L high glucose media for 48 h to mimic the DN environment in vitro. Gene and protein expressions were determined by quantitative real-time PCR and Western blot. Cell viability and pyroptosis were measured by MTT assay and flow cytometry analysis, respectively. The relationship between lncRNA NEAT1, miR-34c, and Nod-like receptor protein-3 (NLRP3) was confirmed by luciferase reporter assay. Results: We found that upregulation of NEAT1 was associated with the increase of pyroptosis in DN models. miR-34c, as a target gene of NEAT1, mediated the effect of NEAT1 on pyroptosis in DN by regulating the expression of NLRP3 as well as the expressions of caspase-1 and interleukin-1β. Either miR-34c inhibition or NLRP3 overexpression could reverse the accentuation of pyroptosis and inflammation by sh-NEAT1 transfection in the in vitro model of DN. Conclusions: Our findings suggested NEAT1 and its target gene miR-34c regulated cell pyroptosis via mediating NLRP3 in DN, providing new insights into understanding the molecular mechanisms of pyroptosis in the pathogenesis of DN.

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Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c/NLRP3 Axis

Zhan¹,

Huang²,

Huang³

et al. 2020

Kidney Blood Press Res

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“…NLRP3 was also reported to be involved in kidney injury, including renal I/R injury. It was demonstrated that NLRP3/E3 ubiquitin-protein ligase XIAP signaling aggravated renal fibrotic injury, and also NLRP3 inflammasome activation negatively regulated podocyte autophagy in diabetic nephropathy ( 10 , 11 ). Additionally, a humanized IL-6 receptor (IL-6R) antibody could reduce the activation of NLRP3 inflammasome in diabetic nephropathy, partly via suppressing IL-17A, which could be suppressed by neutralization of IL-17C in renal I/R ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Tetramethylpyrazine alleviates acute kidney injury by inhibiting NLRP3/HIF‑1α and apoptosis

Sun

Wang

et al. 2020

Mol Med Rep

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The aim of the present study was to investigate the protective effect and underlying mechanism of tetramethylpyrazine (TMP) on renal ischemia reperfusion injury (RIRI) in rats, which refers to the injury caused by the restoration of blood supply and reperfusion of the kidney after a period of ischemia. Sprague-Dawley rats were randomly divided into a Sham group, renal ischemia-reperfusion (I/R) group and TMP group. TMP hydrochloride (40 mg/kg, 6 h intervals) was given via intraperitoneal injection immediately after reperfusion in the TMP group, after 24 h the kidney tissues were taken for follow-up experiments. Pathological changes in the kidney tissues were observed by periodic acid-Schiff staining. Renal function was assessed by measuring levels of serum creatinine and blood urea nitrogen, and inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. Renal cell apoptosis was detected by TUNEL-DAPI double staining, mRNA and protein changes were analyzed by reverse transcription-quantitative PCR and western blotting. Cell viability was measured using a CCK-8 assay. It was found that the renal tissues of the sham operation group were notably abnormal, and the renal tissues of the I/R group were damaged, while the renal tissues of the TMP group were less damaged compared with those of the I/R group. Compared with the I/R group, the serum creatinine and blood urea nitrogen levels in the TMP group were low (all P<0.05), levels of inflammatory cytokines TNF-α and IL-6 decreased, the apoptotic rate was low (all P<0.05), and the relative expression levels of nucleotide-oligomerization domain-like receptor 3 (NLRP3) protein and mRNA in renal tissues were low (all P<0.05). The expression levels of hypoxia-inducible factor 1-α and NLRP3 increased after oxygen and glucose deprivation (OGD), and reduced after treatment with OGD and TMP (all P<0.05). It was concluded that TMP can reduce renal injury and improve renal function in RIRI rats, and its mechanism may be related to the reduction of NLRP3 expression in renal tissues.

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“…These proteins play a key role in the control of inflammatory and immune responses through the modulation of different signaling pathways, including those dependent on nuclear factor (NF)-κB and the caspase-1-mediated cleavage of interleukin (IL)-1β and IL-18, respectively (6,7). Moreover, NOd2 and NLRP3 are extensively involved in the progression of renal diseases (8)(9)(10)(11)(12). Suppression of NOd2-mediated immune responses was found to attenuate hypoxia-induced…”

Section: Introductionmentioning

confidence: 99%

Ligustrazine ameliorates acute kidney injury through downregulation of NOD2‑mediated inflammation

et al. 2020

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Ligustrazine has been used to alleviate clinical acute kidney injury (AKI); however, the underlying molecular mechanisms are poorly understood. In order to further elucidate the molecular mechanism underlying its occurrence, the role of nucleotide-binding oligomerization domain-containing 2 (NOd2) in AKI was investigated in the present study, and the results indicated that ligustrazine exerts an important protective effect against AKI in vivo by inhibiting the upregulation of NOd2 expression and reducing apoptosis of kidney cells following ischemia/reperfusion injury in rat models. Furthermore, the inhibitory role of ligustrazine on the upregulation of NOd2 and apoptosis of kidney cells induced by cocl 2 and oxygen and glucose deprivation followed by reoxygenation was investigated in in vitro experiments. The effect of ligustrazine on NOd2 downregulation was partially blocked by inhibiting autophagy. To the best of our knowledge, the results of the present study are the first to provide evidence that ligustrazine can inhibit NOD2-mediated inflammation to protect against renal injury, which may be in part attributed to the induction of autophagy. These findings may help design and develop new approaches and therapeutic strategies for AKI to prevent the deterioration of renal function.

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Apocynin inhibited NLRP3/XIAP signalling to alleviate renal fibrotic injury in rat diabetic nephropathy

Cited by 38 publications

References 49 publications

Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c/NLRP3 Axis

Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c/NLRP3 Axis

Tetramethylpyrazine alleviates acute kidney injury by inhibiting NLRP3/HIF‑1α and apoptosis

Ligustrazine ameliorates acute kidney injury through downregulation of NOD2‑mediated inflammation

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