Knockdown of PHLDA1 Alleviates Necrotizing Enterocolitis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Through Enhancing Nrf2 Signaling

Yang, Xin; Li, Xihong; Wu, Chan; Zhang, Feng

doi:10.1080/08820139.2022.2161910

Cited by 5 publications

(8 citation statements)

References 29 publications

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“…Research has found that Phlda1 was crucial in inflammation and pyroptosis [30]. Yang et al discovered that by knocking down Phlda1, pyroptosis could be inhibited through the enhancement of Nrf2 signaling [19]. Shu et al demonstrated that Phlda1 enhanced pyroptosis in rat neonatal cells induced by sevoflurane via TRAF6mediated activation of Rac1 [18].…”

Section: Discussionmentioning

confidence: 99%

“…Yang et al . discovered that by knocking down Phlda1, pyroptosis could be inhibited through the enhancement of Nrf2 signaling [19]. Shu et al .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have found a close association between Phlda1 and neuronal pyroptosis [18,19]. Since we have found that both Egr1 and Phlda1 were observably highly expressed in hemin-induced neurons, we further explored the relationship between these two molecules.…”

Section: Phlda1 Was Transcriptionally Activated By Egr1mentioning

confidence: 92%

“…Nonetheless, the function of Phlda1 in brain damage caused by ICH remains undefined. Notably, Phlda1 has been identified as a facilitator of neuronal pyroptosis [18,19]. This leads to speculation about a possible correlation between Phlda1 and Nlrc4-mediated neuronal pyroptosis in ICH.…”

Section: Introductionmentioning

confidence: 99%

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Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

Wang,

Gu,

Jin

et al. 2024

NeuroReport

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Intracerebral hemorrhage (ICH) is a fatal brain injury, but the current treatments for it are inadequate to reduce the severity of secondary brain injury. Our study aims to explore the molecular mechanism of Egr1 and Phlda1 in regulating hemin-induced neuronal pyroptosis, and hope to provide novel therapeutic targets for ICH treatment. Mouse hippocampal neuron cells treated with hemin were used to simulate an in-vitro ICH model. Using qRT-PCR and western blot to evaluate mRNA and protein concentrations. MTT assay was utilized to assess cell viability. LDH levels were determined by lactate Dehydrogenase Activity Assay Kit. IL-1β and IL-18 levels were examined by ELISA. The interaction of Egr1 and Phlda1 promoter was evaluated using chromatin immunoprecipitation and dual-luciferase reporter assays. Egr1 and Phlda1 were both upregulated in HT22 cells following hemin treatment. Hemin treatment caused a significant reduction in HT22 cell viability, an increase in Nlrc4 and HT22 cell pyroptosis, and heightened inflammation. However, knocking down Egr1 neutralized hemin-induced effects on HT22 cells. Egr1 bound to the promoter of Phlda1 and transcriptionally activated Phlda1. Silencing Phlda1 significantly reduced Nlrc4-dependent neuronal pyroptosis. Conversely, overexpressing Phlda1 mitigated the inhibitory effects of Egr1 knockdown on Nlrc4 and neuronal pyroptosis during ICH. Egr1 enhanced neuronal pyroptosis mediated by Nlrc4 under ICH via transcriptionally activating Phlda1.

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Section: Discussionmentioning

confidence: 99%

“…Yang et al . discovered that by knocking down Phlda1, pyroptosis could be inhibited through the enhancement of Nrf2 signaling [19]. Shu et al .…”

Section: Discussionmentioning

confidence: 99%

Section: Phlda1 Was Transcriptionally Activated By Egr1mentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

Wang,

Gu,

Jin

et al. 2024

NeuroReport

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“…Recently, PHLDA1 was found to be highly expressed in the intestinal tissues of NEC mice. In sh-PHLDA1 transfected mice with NEC, the survival rate was increased, and intestinal inflammation, oxidative stress, and cell scorching were also improved significantly ( 57 ). Knockdown of PHLDA1 was shown to alleviate the NEC phenotype by activating Nrf2 to inhibit NLRP3 activation and pyroptosis ( 57 ).…”

Section: Death Of Iecsmentioning

confidence: 99%

Programmed death of intestinal epithelial cells in neonatal necrotizing enterocolitis: a mini-review

Yang

Wei

Zhong³

et al. 2023

Front. Pediatr.

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Necrotizing enterocolitis (NEC) is one of the most fatal diseases in premature infants. Damage to the intestinal epithelial barrier (IEB) is an important event in the development of intestinal inflammation and the evolution of NEC. The intestinal epithelial monolayer formed by the tight arrangement of intestinal epithelial cells (IECs) constitutes the functional IEB between the organism and the extra-intestinal environment. Programmed death and regenerative repair of IECs are important physiological processes to maintain the integrity of IEB function in response to microbial invasion. However, excessive programmed death of IECs leads to increased intestinal permeability and IEB dysfunction. Therefore, one of the most fundamental questions in the field of NEC research is to reveal the pathological death process of IECs, which is essential to clarify the pathogenesis of NEC. This review focuses on the currently known death modes of IECs in NEC mainly including apoptosis, necroptosis, pyroptosis, ferroptosis, and abnormal autophagy. Furthermore, we elaborate on the prospect of targeting IECs death as a treatment for NEC based on exciting animal and clinical studies.

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Biliverdin modulates the Nrf2/A20/eEF1A2 axis to alleviate cerebral ischemia-reperfusion injury by inhibiting pyroptosis

Bai

Huo

Zhou

et al. 2023

Biomedicine & Pharmacotherapy

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Knockdown of PHLDA1 Alleviates Necrotizing Enterocolitis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Through Enhancing Nrf2 Signaling

Cited by 5 publications

References 29 publications

Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

Programmed death of intestinal epithelial cells in neonatal necrotizing enterocolitis: a mini-review

Biliverdin modulates the Nrf2/A20/eEF1A2 axis to alleviate cerebral ischemia-reperfusion injury by inhibiting pyroptosis

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