Geranylgeranyl diphosphate synthase 1 knockdown suppresses NLRP3 inflammasome activity via promoting autophagy in sepsis-induced acute lung injury

Li, Dahuan; Li, Chunyan; Wang, Tianzhong; Zhang, Chong; Zhu, Zhen; Zhang, Guoxiu; Fang, Bangjiang

doi:10.1016/j.intimp.2021.108106

Cited by 10 publications

(9 citation statements)

References 32 publications

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“… 27 In addition, Geranylgeranyl pyrophosphate synthase large subunit (GGPPS1) has also been shown to be effective against sepsis-induced acute lung injury by suppressing NLRP3 inflammasome activity in the TLR4-NFκB pathway. 82 , 83 Consistent with the previous finding, Ghrelin, a hormone protective against neuronal injury and stroke, has been shown to alleviate brain injury induced by acute lung injury by blocking the TLR4-NFκB signaling pathway. 28 Therapeutic targets in LPS-induced acute lung injury through pyroptosis have been heavily studied, showing promising results in inhibiting lung injury and pulmonary inflammation ( Table 1 ).…”

Section: Overview Of Pyroptosis and Gasdermin-dsupporting

confidence: 85%

The Role of Gasdermin-D-Mediated Pyroptosis in Organ Injury and Its Therapeutic Implications

2023

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Gasdermin-D (GSDMD) belongs to the Gasdermin family (GSDM), which are pore-forming effector proteins that facilitate inflammatory cell death, also known as pyroptosis. This type of programmed cell death is dependent on inflammatory caspase activation, which cleaves gasdermin-D (GSDMD) to form membrane pores and initiates the release of pro-inflammatory cytokines. Pyroptosis plays an important role in achieving immune regulation and homeostasis within various organ systems. The role of GSDMD in pyroptosis has been extensively studied in recent years. In this review, we summarize the role of GSDMD in cellular and organ injury mediated by pyroptosis. We will also provide an outlook on GSDMD therapeutic targets in various organ systems.

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Section: Overview Of Pyroptosis and Gasdermin-dsupporting

confidence: 85%

The Role of Gasdermin-D-Mediated Pyroptosis in Organ Injury and Its Therapeutic Implications

2023

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“…The knocking-down of GGPPS1 gene enhanced alveolar macrophage autophagy, as evidenced by an increase in the LCII/LCI ratio, decrease in p62 expression, and significant reduction of the expression of NLRP3 protein. These findings indicate that GGPPS1 knockdown can alleviate sepsis-induced lung injury by promoting autophagy to induce NLRP3 inflammasome inactivation ( 120 ).…”

Section: Macrophage Autophagy and Ali/ardsmentioning

confidence: 95%

Progress in preclinical studies of macrophage autophagy in the regulation of ALI/ARDS

2022

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Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical clinical syndrome with high morbidity and mortality that poses a major challenge in critical care medicine. The development of ALI/ARDS involves excessive inflammatory response, and macrophage autophagy plays an important role in regulating the inflammatory response in ALI/ARDS. In this paper, we review the effects of autophagy in regulating macrophage function, discuss the roles of macrophage autophagy in ALI/ARDS, and highlight drugs and other interventions that can modulate macrophage autophagy in ALI/ARDS to improve the understanding of the mechanism of macrophage autophagy in ALI/ARDS and provide new ideas and further research directions for the treatment of ALI/ARDS.

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“… 58 Further studies found that inhibition of NLRP3 inflammasome by GGDPS inhibition resulted in promotion of autophagy, allowing for attenuation of sepsis‐induced lung injury. 59 Similarly, knockdown of the enzyme also inhibited migration and invasion of lung adenocarcinoma cancer cells. 61 …”

Section: Knockout Models Of Ggdpsmentioning

confidence: 96%

“…In both mouse models, lung‐specific deletion of GGPS1 attenuated disease symptoms. 58 , 59 , 60 Deletion of GGPS1 reduced Rab10 membrane localisation which led to decreased activation of TLR4–NF‐κB signaling. 58 NF‐ κB is a necessary transcription factor for NLRP3 activation, therefore by inhibiting this pathway, NLRP3 inflammasome transcription was inhibited, attenuating disease‐induced lung inflammation.…”

Section: Knockout Models Of Ggdpsmentioning

confidence: 99%

“…NF‐ κB is a necessary transcription factor for NLRP3 activation, therefore by inhibiting this pathway, NLRP3 inflammasome transcription was inhibited, attenuating disease‐induced lung inflammation 58 . Further studies found that inhibition of NLRP3 inflammasome by GGDPS inhibition resulted in promotion of autophagy, allowing for attenuation of sepsis‐induced lung injury 59 . Similarly, knockdown of the enzyme also inhibited migration and invasion of lung adenocarcinoma cancer cells 61 …”

Section: Knockout Models Of Ggdpsmentioning

confidence: 99%

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Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target

Muehlebach

Holstein

2023

Clinical & Translational Med

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Geranylgeranyl diphosphate synthase (GGDPS), an enzyme in the isoprenoid biosynthesis pathway, is responsible for the production of geranylgeranyl pyrophosphate (GGPP). GGPP serves as a substrate for the post‐translational modification (geranylgeranylation) of proteins, including those belonging to the Ras superfamily of small GTPases. These proteins play key roles in signalling pathways, cytoskeletal regulation and intracellular transport, and in the absence of the prenylation modification, cannot properly localise and function. Aberrant expression of GGDPS has been implicated in various human pathologies, including liver disease, type 2 diabetes, pulmonary disease and malignancy. Thus, this enzyme is of particular interest from a therapeutic perspective. Here, we review the physiological function of GGDPS as well as its role in pathophysiological processes. We discuss the current GGDPS inhibitors under development and the therapeutic implications of targeting this enzyme.

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Geranylgeranyl diphosphate synthase 1 knockdown suppresses NLRP3 inflammasome activity via promoting autophagy in sepsis-induced acute lung injury

Cited by 10 publications

References 32 publications

The Role of Gasdermin-D-Mediated Pyroptosis in Organ Injury and Its Therapeutic Implications

The Role of Gasdermin-D-Mediated Pyroptosis in Organ Injury and Its Therapeutic Implications

Progress in preclinical studies of macrophage autophagy in the regulation of ALI/ARDS

Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target

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