Usp25 Upregulation Boosts GSDMD-Mediated Pyroptosis of Acinar Cells in Acute Pancreatitis

Lv, Hui; Liu, Xuejin; Zhang, Hongtao

doi:10.1097/shk.0000000000001992

Cited by 6 publications

(4 citation statements)

References 57 publications

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“…USP25 is a DUB that is encoded by a gene located at 21q11.2. [21] Functionally, USP25 has been shown to participate in multiple inflammatory diseases including multiple sclerosis, [11] sepsis, [12] viral infection, [13] colitis, [15] pancreatitis, [14,22] and 24 h. Proteins were immunoprecipitated from whole cell lysates with indicated antibodies and analyzed by western blot. F) A schematic presentation of USP25 and different mutants.…”

Section: Discussionmentioning

confidence: 99%

“…USP25 is a DUB that is encoded by a gene located at 21q11.2. [ 21 ] Functionally, USP25 has been shown to participate in multiple inflammatory diseases including multiple sclerosis, [ 11 ] sepsis, [ 12 ] viral infection, [ 13 ] colitis, [ 15 ] pancreatitis, [ 14 , 22 ] and Alzheimer's disease (AD). [ 16 ] In addition to inflammatory diseases, USP25 has emerged as a key regulator in cancer.…”

Section: Discussionmentioning

confidence: 99%

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USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

Li,

Liu,

Lambertsen

et al. 2023

Advanced Science

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Cerebral ischemic stroke is a leading cause of morbidity and mortality globally. However, the mechanisms underlying ischemic stroke injury remain poorly understood. Here, it is found that deficiency of the ubiquitin‐specific protease USP25 significantly aggravate ischemic stroke injury in mice. USP25 has no impact on neuronal death under hypoxic conditions, but reduced ischemic stroke‐induced neuronal loss and neurological deficits by inhibiting microglia‐mediated neuroinflammation. Mechanistically, USP25 restricts the activation of NF‐κB and MAPK signaling by regulating TAB2. As a deubiquitinating enzyme, USP25 removeds K63‐specific polyubiquitin chains from TAB2. AAV9‐mediated TAB2 knockdown ameliorates ischemic stroke injury and abolishes the effect of USP25 deletion. In both mouse and human brains, USP25 is markedly upregulated in microglia in the ischemic penumbra, implying a clinical relevance of USP25 in ischemic stroke. Collectively, USP25 is identified as a critical inhibitor of ischemic stroke injury and this data suggest USP25 may serve as a therapeutic target for ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

“…USP25 is a DUB that is encoded by a gene located at 21q11.2. [ 21 ] Functionally, USP25 has been shown to participate in multiple inflammatory diseases including multiple sclerosis, [ 11 ] sepsis, [ 12 ] viral infection, [ 13 ] colitis, [ 15 ] pancreatitis, [ 14 , 22 ] and Alzheimer's disease (AD). [ 16 ] In addition to inflammatory diseases, USP25 has emerged as a key regulator in cancer.…”

Section: Discussionmentioning

confidence: 99%

USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

Li,

Liu,

Lambertsen

et al. 2023

Advanced Science

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“…GSDMs-mediated pathways are regulated by various molecules, such as miRNAs, oxidative stress, chemokines (83)(84)(85)(86). Activated GSDMs proteins bound to the plasma membrane and formed pores (87), mediating cell death or inflammatory factors release, functional proteins, etc.…”

Section: Gsdms-mediated Pathway Except Caspases and Granzymesmentioning

confidence: 99%

Gasdermins in sepsis

Wang,

2023

Front. Immunol.

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Sepsis is a hyper-heterogeneous syndrome in which the systemic inflammatory response persists throughout the course of the disease and the inflammatory and immune responses are dynamically altered at different pathogenic stages. Gasdermins (GSDMs) proteins are pore-forming executors in the membrane, subsequently mediating the release of pro-inflammatory mediators and inflammatory cell death. With the increasing research on GSDMs proteins and sepsis, it is believed that GSDMs protein are one of the most promising therapeutic targets in sepsis in the future. A more comprehensive and in-depth understanding of the functions of GSDMs proteins in sepsis is important to alleviate the multi-organ dysfunction and reduce sepsis-induced mortality. In this review, we focus on the function of GSDMs proteins, the molecular mechanism of GSDMs involved in sepsis, and the regulatory mechanism of GSDMs-mediated signaling pathways, aiming to provide novel ideas and therapeutic strategies for the diagnosis and treatment of sepsis.

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“…USP25 has been proved to play either pro-inflammatory or anti-inflammation role in different conditions [ 5 , 10 , 11 ]. Noticeably, USP25 upregulation was reported to boost NLRP3 inflammasome-mediated pyroptosis of acinar cells in acute pancreatitis [ 12 ]. Therefore, we speculated that USP25 may mediate inflammation in OA, probably through its interaction with the NLRP3 inflammasome.…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin-specific peptidase 25 exacerbated osteoarthritis progression through facilitating TXNIP ubiquitination and NLRP3 inflammasome activation

Sui,

Dai,

Shi

et al. 2023

J Orthop Surg Res

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Several members of the ubiquitin-specific proteases (USPs) family have been revealed to regulate the progression of osteoarthritis (OA). The current study aimed to investigate the role and the underlying mechanism of USP25 in IL-1β-induced chondrocytes and OA rat model. It was discovered that IL-1β stimulation upregulated USP25, increased ROS level, and suppressed cell viability in rat chondrocytes. Besides, USP25 knockdown alleviated IL-1β-induced injury by decreasing ROS level, attenuating pyroptosis, and downregulating the expression of IL-18, NLRP3, GSDMD-N, active caspase-1, MMP-3, and MMP-13. Furthermore, we discovered that USP25 affected the IL-1β-induced injury in chondrocytes in a ROS-dependent manner. Moreover, USP25 was revealed to interact with TXNIP, and USP25 knockdown increased the ubiquitination of TXNIP. The pro-OA effect of USP25 abundance could be overturned by TXNIP suppression in IL-1β-induced chondrocytes. Finally, in vivo experiment results showed that USP25 inhibition alleviated cartilage destruction in OA rats. In conclusion, we demonstrated that USP25 stimulated the overproduction of ROS to activate the NLRP3 inflammasome via regulating TXNIP, resulting in increased pyroptosis and inflammation in OA.

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Usp25 Upregulation Boosts GSDMD-Mediated Pyroptosis of Acinar Cells in Acute Pancreatitis

Cited by 6 publications

References 57 publications

USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

Gasdermins in sepsis

Ubiquitin-specific peptidase 25 exacerbated osteoarthritis progression through facilitating TXNIP ubiquitination and NLRP3 inflammasome activation

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