Pristimerin suppresses AIM2 inflammasome by modulating AIM2-PYCARD/ASC stability via selective autophagy to alleviate tendinopathy

Jiang, Huaji; Xie, Yingchao; Lu, Jiansen; Li, Hongyu; Zeng, Ke; Hu, Zhiqiang; Wu, Dan; Yang, Jianwu; Yao, Zhenxia; Chen, Huadan; Gong, Xiaoqian; Yu, Xiao

doi:10.1080/15548627.2023.2249392

Cited by 8 publications

(5 citation statements)

References 75 publications

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“…Accumulating evidence has shown that ubiquitination of cargoes serves as a critical recognition signal during selective autophagy [ 65 ]. In the process of inflammasome activation, key inflammasome components, including NLRP3, ASC, and AIM2, could undergo ubiquitination, which are sensed by different cargo receptors for selective autophagy [ 61 , 64 , 66 ]. As the central pyroptosis executioner during inflammasome activation, GSDMD has been revealed to undergo ubiquitination, but the participation of cargo receptors on GSDMD stability remained to be investigated.…”

Section: Discussionmentioning

confidence: 99%

USP18 Antagonizes Pyroptosis by Facilitating Selective Autophagic Degradation of Gasdermin D

Wang,

Li,

Lian

et al. 2024

Research

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As a key executioner of pyroptosis, Gasdermin D (GSDMD) plays a crucial role in host defense and emerges as an essential therapeutic target in the treatment of inflammatory diseases. So far, the understanding of the mechanisms that regulate the protein level of GSDMD to prevent detrimental effects and maintain homeostasis is currently limited. Here, we unveil that ubiquitin-specific peptidase 18 (USP18) works as a negative regulator of pyroptosis by targeting GSDMD for degradation and preventing excessive innate immune responses. Mechanically, USP18 recruits E3 ubiquitin ligase mind bomb homolog 2 (MIB2) to catalyze ubiquitination on GSDMD at lysine (K) 168, which acts as a recognition signal for the selective autophagic degradation of GSDMD. We further confirm the alleviating effect of USP18 on LPS-triggered inflammation in vivo. Collectively, our study demonstrates the role of USP18 in regulating GSDMD-mediated pyroptosis and reveals a previously unknown mechanism by which GSDMD protein level is rigorously controlled by selective autophagy.

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Section: Discussionmentioning

confidence: 99%

USP18 Antagonizes Pyroptosis by Facilitating Selective Autophagic Degradation of Gasdermin D

Wang,

Li,

Lian

et al. 2024

Research

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“…The AIM2 inflammasome is a part of the innate immune system and plays a crucial role in recognizing and responding to cytosolic DNA (H. Jiang et al, 2023). The inflammasome is a multiprotein complex that serves as a platform for the activation of inflammatory caspases, particularly caspase-1 (Y.…”

Section: The Main Biological Functions Of the Aim2 Inflammasomementioning

confidence: 99%

“…The AIM2 inflammasome is activated in response to the presence of dsDNA in the cytoplasm . This DNA can be of microbial origin (from pathogens) or host DNA released during cellular stress or damage (H. Jiang et al, 2023). Furthermore, AIM2 inflammasomes can be recruited into the nucleus as well as operating in the cytoplasm (Hu et al, 2016).…”

Section: Recognition Of Cytosolic Dnamentioning

confidence: 99%

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The cytoplasmic sensor, the AIM2 inflammasome: A precise therapeutic target in vascular and metabolic diseases

Lin,

Wang,

Fang

et al. 2024

British J Pharmacology

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Cardio‐cerebrovascular diseases encompass pathological changes in the heart, brain and vascular system, which pose a great threat to health and well‐being worldwide. Moreover, metabolic diseases contribute to and exacerbate the impact of vascular diseases. Inflammation is a complex process that protects against noxious stimuli but is also dysregulated in numerous so‐called inflammatory diseases, one of which is atherosclerosis. Inflammation involves multiple organ systems and a complex cascade of molecular and cellular events. Numerous studies have shown that inflammation plays a vital role in cardio‐cerebrovascular diseases and metabolic diseases. The absent in melanoma 2 (AIM2) inflammasome detects and is subsequently activated by double‐stranded DNA in damaged cells and pathogens. With the assistance of the mature effector molecule caspase‐1, the AIM2 inflammasome performs crucial biological functions that underpin its involvement in cardio‐cerebrovascular diseases and related metabolic diseases: The production of interleukin‐1 beta (IL-1β), interleukin‐18 (IL-18) and N‐terminal pore‐forming Gasdermin D fragment (GSDMD‐N) mediates a series of inflammatory responses and programmed cell death (pyroptosis and PANoptosis). Currently, several agents have been reported to inhibit the activity of the AIM2 inflammasome and have the potential to be evaluated for use in clinical settings. In this review, we systemically elucidate the assembly, biological functions, regulation and mechanisms of the AIM2 inflammasome in cardio‐cerebrovascular diseases and related metabolic diseases and outline the inhibitory agents of the AIM2 inflammasome as potential therapeutic drugs.

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“… 28 Jiang et al found that pristimerin alleviated tendinopathy by promoting autophagy and regulating the stability of AIM2-PYCARD/ASC. 29 However, the opposite situation also exists; pristimerin inhibited autophagy, down-regulated the expression levels of LC3-II and beclin1, and enhanced the sensitivity of A549 and NCI-H446 cells to cisplatin ( Table 1 and Figure 2 ). 30 …”

Section: Introductionmentioning

confidence: 99%

Pristimerin Exerts Pharmacological Effects Through Multiple Signaling Pathways: A Comprehensive Review

Sun,

Tian,

et al. 2024

DDDT

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Pristimerin, a natural triterpenoid isolated from the plants of southern snake vine and Maidenwood in the family Weseraceae, is anti-inflammatory, insecticidal, antibacterial, and antiviral substance and has been used for its cardioprotective and antitumor effects and in osteoporosis treatment. These qualities explain Pristimerin's therapeutic effects on different types of tumors and other diseases. More and more studies have shown that pristimerin acts in a wide range of biological activities and has shown great potential in various fields of modern and Chinese medicine. While Pristimerin's wide range of pharmacological effects have been widely studied by others, our comprehensive review suggests that its mechanism of action may be through affecting fundamental cellular events, including blocking the cell cycle, inducing apoptosis and autophagy, and inhibiting cell migration and invasion, or through activating or inhibiting certain key molecules in several cell signaling pathways, including nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/protein kinase B/mammalian-targeted macromycin (PI3K/Akt/mTOR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 1/2 (ERK1/2), Jun amino-terminal kinase (JNK1/2/3), reactive oxygen species (ROS), wingless/integrin1 (Wnt)/β-catenin, and other signaling pathways. This paper reviews the research progress of Pristimerin's pharmacological mechanism of action in recent years to provide a theoretical basis for the molecular targeting therapy and further development and utilization of Pristimerin. It also provides insights into improved treatments and therapies for clinical patients and the need to explore pristimerin as a potential facet of treatment.

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Pristimerin suppresses AIM2 inflammasome by modulating AIM2-PYCARD/ASC stability via selective autophagy to alleviate tendinopathy

Cited by 8 publications

References 75 publications

USP18 Antagonizes Pyroptosis by Facilitating Selective Autophagic Degradation of Gasdermin D

USP18 Antagonizes Pyroptosis by Facilitating Selective Autophagic Degradation of Gasdermin D

The cytoplasmic sensor, the AIM2 inflammasome: A precise therapeutic target in vascular and metabolic diseases

Pristimerin Exerts Pharmacological Effects Through Multiple Signaling Pathways: A Comprehensive Review

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