USP25 Deficiency Exacerbates Acute Pancreatitis via Up-Regulating TBK1–NF-κB Signaling in Macrophages

Liu, Xin; Luo, Wei; Hu, Chenghong; Mutsinze, Rumbidzai Natasha; Wang, Xu; Zhang, Yanmei; Huang, Lijiang; Zuo, Wei; Liang, Guang; Wang, Yi

doi:10.1016/j.jcmgh.2022.07.013

Cited by 13 publications

(6 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that USP25 is a DUB that participates in the regulation of various inflammatory diseases [ 11 , 12 , 13 , 14 , 15 ] and that neuroinflammation is also a critical factor underlying ischemic stroke injury, we asked whether USP25 was involved in ischemic stroke injury. We first analyzed the expression of USP25 in mouse brains before and after MCAO and found that both protein and mRNA levels of USP25 were significantly reduced in the brain of MCAO mice ( Figure 1 A–C ), implying a potential involvement of USP25 in ischemic stroke.…”

Section: Resultsmentioning

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 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%

“…For example, USP25 inhibits experimental autoimmune encephalomyelitis by inhibiting IL‐17‐induced signaling and inflammation. [ 11 ] In addition, USP25 is also involved in other inflammation‐associated diseases including sepsis, [ 12 ] viral infection, [ 13 ] pancreatitis, [ 14 ] colitis, [ 15 ] and Alzheimer's disease. [ 16 ] However, the function of USP25 in stroke has not been studied.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

Li,

Liu,

Lambertsen

et al. 2023

Advanced Science

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

Li,

Liu,

Lambertsen

et al. 2023

Advanced Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is also worthwhile to conduct related research to further expand the function of USP25, which could provide some preliminary experimental basis for the research and development of drugs targeting USP25 in cardiovascular diseases. Previous studies have shown that USP25 is involved in the pathogenesis of experimental colitis or bacterial infections, 12 pancreatitis, 36 and LPS-induced sepsis 37,38 by regulating inflammatory signaling pathway. Meanwhile, it has also been reported that chronic inflammation is involved in Ang II-induced cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that USP25 is involved in the pathogenesis of experimental colitis or bacterial infections, 12 pancreatitis, 36 and LPS-induced sepsis 37,38 by regulating inflammatory signaling pathway. Meanwhile, it has also been reported that chronic inflammation is involved in Ang II-induced cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

USP25 Ameliorates Pathological Cardiac Hypertrophy by Stabilizing SERCA2a in Cardiomyocytes

Zhou

Chen

et al. 2023

Circulation Research

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Pathological cardiac hypertrophy can lead to heart failure and is one of the leading causes of death globally. Understanding the molecular mechanism of pathological cardiac hypertrophy will contribute to the treatment of heart failure. DUBs (deubiquitinating enzymes) are essential to cardiac pathophysiology by precisely controlling protein function, localization, and degradation. This study set out to investigate the role and molecular mechanism of a DUB, USP25 (ubiquitin-specific peptidase 25), in pathological cardiac hypertrophy. METHODS: The role of USP25 in myocardial hypertrophy was evaluated in murine cardiomyocytes in response to Ang II (angiotensin II) and transverse aortic constriction stimulation and in hypertrophic myocardium tissues of heart failure patients. Liquid chromotography with mass spectrometry/mass spectrometry analysis combined with Co-IP was used to identify SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2A), an antihypertrophy protein, as an interacting protein of USP25. To clarify the molecular mechanism of USP25 in the regulation of SERCA2a, we constructed a series of mutant plasmids of USP25. In addition, we overexpressed USP25 and SERCA2a in the heart with adenoassociated virus serotype 9 vectors to validate the biological function of USP25 and SERCA2a interaction. RESULTS: We revealed increased protein level of USP25 in murine cardiomyocytes subject to Ang II and transverse aortic constriction stimulation and in hypertrophic myocardium tissues of patients with heart failure. USP25 deficiency aggravated cardiac hypertrophy and cardiac dysfunction under Ang II and transverse aortic constriction treatment. Mechanistically, USP25 bound to SERCA2a directly via its USP (ubiquitin-specific protease) domain and cysteine at position 178 of USP25 exerts deubiquitination to maintain the stability of the SERCA2a protein by removing the K48 ubiquitin chain and preventing proteasomal pathway degradation, thereby maintaining calcium handling in cardiomyocytes. Moreover, restoration of USP25 expression via adenoassociated virus serotype 9 vectors in USP25 −/− mice attenuated Ang II-induced cardiac hypertrophy and cardiac dysfunction, whereas myocardial overexpression of SERCA2a could mimic the effect of USP25. CONCLUSIONS: We confirmed that USP25 inhibited cardiac hypertrophy by deubiquitinating and stabilizing SERCA2a.

show abstract

Long non-coding RNA MM2P suppresses M1-polarized macrophages-mediated excessive inflammation to prevent sodium taurocholate-induced acute pancreatitis by blocking SHP2-mediated STAT3 dephosphorylation

et al. 2023

View full text Add to dashboard Cite

USP25 Deficiency Exacerbates Acute Pancreatitis via Up-Regulating TBK1–NF-κB Signaling in Macrophages

Cited by 13 publications

References 63 publications

USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

USP25 Ameliorates Pathological Cardiac Hypertrophy by Stabilizing SERCA2a in Cardiomyocytes

Long non-coding RNA MM2P suppresses M1-polarized macrophages-mediated excessive inflammation to prevent sodium taurocholate-induced acute pancreatitis by blocking SHP2-mediated STAT3 dephosphorylation

Contact Info

Product

Resources

About