VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
·
2025
·
IF 1.4
Chanyu Wu,Xiaohan Wang,Xincan Li,Hexian Li,Qiuyue Peng,Xiaoxin Niu,Yutong Wu,Zhiying Wang,Zuoyong Zhou
Corynebacterium pseudotuberculosis , a zoonotic intracellular bacteria, is responsible for abscesses and pyogranuloma formation of the infected host, which is essentially a chronic inflammatory response. Tripartite motif-containing protein 21 (TRIM21) negatively regulates pro-inflammatory cytokines production during C . pseudotuberculosis infection, the mechanism of which remains unclear. This study found that C . pseudotuberculosis infection in macrophages induced phosphorylation of IκB and p65. TRIM21 interacted with IκBα by PRY/SPRY domain, stabilizes IκBα and negatively regulates IκBα phosphorylation in macrophages during C. pseudotuberculosis infection. In addition, TRIM21 positively regulates the ubiquitination of IκBα via K48 linkage rather than K63 linkage in C. pseudotuberculosis -infected macrophages. In brief, our research confirmed that TRIM21 negatively regulates canonical NF-κB activation by interacting with IκBα and decreasing IκBα phosphorylation in macrophages during C. pseudotuberculosis infection. Preventing inflammation induced by C. pseudotuberculosis infection through regulation of the NF-κB pathway is a potential way to control this pathogen.
研究领域:
免疫学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Liming Hou,Xiaoming Wang,Min Bai,Qian Li,Wei Zhang,Hui Su,Yan Liu
Myocardial ischemia–reperfusion (MI/R) injury represents a significant complication associated with reperfusion therapy for myocardial infarction. Leucine-rich repeat-containing protein 8A (LRRC8A), a volume-regulated anion channel protein, involved in cellular homeostasis, has been implicated in the progression of cardiovascular events, but its role in MI/R remains uninvestigated. Here, we sought to characterize the role of LRRC8A in MI/R injury and uncover its potential mechanism. A rat MI/R model was developed via left anterior descending coronary artery ligation for 45 min followed by 4 h reperfusion to assess changes in LRRC8A expression in the myocardium. The results revealed that LRRC8A was upregulated in rat hearts after MI/R injury. To silence LRRC8A expression, we injected adenovirus encoding LRRC8A shRNA into the myocardium of MI/R rats 3 days before ischemic surgery. We observed that LRRC8A silencing in post-MI/R rats reduced myocardial infarct area, suppressed cardiomyocyte apoptosis and enhanced cardiac function. Furthermore, rat H9c2 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate MI/R injury in vivo , and the findings indicated that LRRC8A silencing reduced OGD/R-induced cardiomyocyte apoptosis, while its upregulation had an opposite effect, as Bcl-2 expression, Tunel staining demonstrated. Mechanistically, LRRC8A can interact with tripartite motif containing 21 (TRIM21) and subsequently suppress the focal adhesion kinase (FAK)/NF-κB pathway, thereby facilitating cardiomyocyte apoptosis. TRIM21 knockdown eliminated the pro-apoptotic effect of LRRC8A and decreased the inhibitory effect of LRRC8A on the FAK/NF-κB pathway in MI/R rats as well as in OGD/R-exposed cardiomyocytes.
研究领域:
心血管疾病
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biology Direct
·
2024
·Vol. 19
·期 1
·1-18
·
IF 5.7
Liu Xiao-Mei,Wang Zi-Hao,Wei Qian-Xue,Song Yang,Ma Xiao-Xin
Choriocarcinoma is a malignant cancer that belongs to gestational trophoblastic neoplasia (GTN). Herein, serum metabolomic analysis was performed on 29 GTN patients and 30 healthy individuals to characterize the metabolic variations during GTN progression. Ultimately 24 differential metabolites (DMs) were identified, of which, Equol was down-regulated in GTN patients, whose VIP score is the 3rd highest among the 24 DMs. As an intestinal metabolite of daidzein, the anticancer potential of Equol has been demonstrated in multiple cancers, but not choriocarcinoma. Hence, human choriocarcinoma cell lines JEG-3 and Bewo were used and JEG-3-derived subcutaneous xenograft models were developed to assess the effect of Equol on choriocarcinoma. The results suggested that Equol treatment effectively suppressed choriocarcinoma cell proliferation, induced cell apoptosis, and reduced tumorigenesis. Label-free quantitative proteomics showed that 136 proteins were significantly affected by Equol and 20 proteins were enriched in Gene Ontology terms linked to protein degradation. Tripartite motif containing 21 (TRIM21), a E3 ubiquitin ligase, was up-regulated by Equol. Equol-induced effects on choriocarcinoma cells could be reversed by TRIM21 inhibition. Annexin A2 (ANXA2) interacted with TRIM21 and its ubiquitination was modulated by TRIM21. We found that TRIM21 was responsible for proteasome-mediated degradation of ANXA2 induced by Equol, and the inhibitory effects of Equol on the malignant behaviors of choriocarcinoma cells were realized by TRIM21-mediated down-regulation of ANXA2. Moreover, β-catenin activation was inhibited by Equol, which also depended on TRIM21-mediated down-regulation of ANXA2. Taken together, Equol may be a novel candidate for the treatment for choriocarcinoma.Graphical abstract
研究领域:
肿瘤学
·
分子生物学
·
代谢组学
·
蛋白质组学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2024
·Vol. 27
·期 5
·1-10
·
IF 2.4
Jiaqi Shi,Li Chen,Xu Wang,Xin Ma
Steroid‑induced osteonecrosis of the femoral head (ONFH) is a serious complication caused by long‑term or excessive use of glucocorticoids. The present study aimed to ascertain the effects of tripartite motif‑containing protein 21 (TRIM21) on the process of steroid‑induced ONFH and its hidden action mechanism. TRIM21 expression in dexamethasone (Dex)‑treated mouse MC3T3‑E1 preosteoblast cells was examined using reverse transcription‑quantitative PCR and western blotting. The Cell Counting Kit‑8 (CCK‑8) method and lactate dehydrogenase release assay were used to respectively measure cell viability and injury. Flow cytometry analysis was used to assay cell apoptosis. Caspase 3 activity was evaluated using a specific assay, while alkaline phosphatase and Alizarin red S staining were used to evaluate osteogenesis. 2,7‑dichloro‑dihydrofluorescein diacetate fluorescence probe was used to estimate reactive oxygen species generation. Specific assay kits were used to appraise oxidative stress levels. In addition, the expression of apoptosis‑, osteogenic differentiation‑ and Kelch‑like ECH‑associated protein 1 (Keap1)/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling‑associated proteins was assessed using western blotting. In Nrf2 inhibitor (ML385)‑pretreated MC3T3‑E1 cells exposed to Dex, cell apoptosis, osteogenesis and oxidative stress were detected again as aforementioned. Results revealed that TRIM21 expression was raised in Dex‑induced MC3T3‑E1 cells and TRIM21 deletion improved the viability and osteogenic differentiation, whereas it hampered the oxidative stress and apoptosis in MC3T3‑E1 cells with Dex induction. In addition, silencing of TRIM21 activated Keap1/Nrf2 signaling. Moreover, ML385 partially abrogated the effects of TRIM21 depletion on the oxidative stress, apoptosis and osteogenic differentiation in MC3T3‑E1 cells exposed to Dex. In conclusion, TRIM21 silencing might activate Keap1/Nrf2 signaling to protect against steroid‑induced ONFH.
研究领域:
骨科
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF VIROLOGY
·
2024
·Vol. 169
·期 4
·1-10
·
IF 2.5
Yuan Juan,Pan Jianli,Zhang Xiaofang,Gao Rui
Triple motif protein 21 (TRIM21) has an antiviral function that inhibits various viral infections. However, its role in the progress of influenza A virus (IAV) infection is unclear. In this study, we investigated the role and molecular mechanism of TRIM21 in IAV infection. RT-qPCR was used to determine the level of TRIM21 mRNA, and ELISA was used to measure the levels of IFN-α, IFN-β, IL-6, and TNF-α. The levels of the TRIM21, NP, TBK1, IRF3, p-TBK1, and p-IRF3 proteins were estimated by Western blot. The results showed that, after IAV infection, TRIM21 was upregulated in clinical patient serum and A549 cells, and this was correlated with the IFN response. Overexpression of TRIM21 reduced IAV replication and transcription in in vitro cell experiments. TRIM21 also increased IFN-α and IFN-β levels and decreased IL-6 and TNF-α levels in A549 cells. In addition, overexpression of TRIM21 inhibited IAV-induced apoptosis. Further experiments demonstrated that TBK1-IRF3 signaling was activated by TRIM21 and was involved in the inhibitory effect of TRIM21 on virus replication. In summary, our study suggests that TRIM21 inhibits viral replication by activating the TBK1-IRF3 signaling pathway, further inhibiting the infection process of IAV.
CAS / MDL:
研究领域:
病毒学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2026
·Vol. 17
·期 1
·218
·
IF 12.2
Zhang Ziyun,Li Yi,Hu Jingjiang,Tang Xingjie,Li Zhanpeng,Sun Xiaoyan,Feng Dade,Yao Yixin,Mao Chao,Tao Yongguang,Xie Li,Luo Huaiqing,Li Yufei,Yu Xing,Peng Xiaoning,Cong Li,Jiang Yiqun
Oral squamous cell carcinoma (OSCC) is an aggressive malignancy characterized by poor prognosis, largely attributable to cancer stem cell (CSC) persistence and ferroptosis resistance. However, the molecular mechanisms that coordinately regulate stemness maintenance and ferroptosis suppression in OSCC remain insufficiently characterized. In this study, KIF20A was identified as significantly overexpressed in OSCC and strongly correlated with adverse clinical outcomes. An integrative approach identified DHX9 as a candidate interactor of KIF20A. Mechanistic investigations revealed that KIF20A regulates DHX9 nucleocytoplasmic distribution and inhibits TRIM21-mediated K48-linked polyubiquitination at DHX9-K755, thereby preventing its proteasomal degradation and enhancing protein stability. Elevated DHX9 enhanced SOX2 mRNA stability, leading to upregulation of SOX2, a central regulator of both CSC maintenance and ferroptosis resistance. Functionally, KIF20A promoted CSC phenotypes, inhibited ferroptosis in vitro and in vivo, and activated the PI3K/AKT signaling pathway. Notably, treatment with ENMD-2076 (identified through Connectivity Map analysis) significantly reduced KIF20A expression, attenuated CSC characteristics, augmented cisplatin sensitivity, and exerted marked antitumor activity. These findings elucidate a novel KIF20A-DHX9-SOX2 regulatory axis that simultaneously governs CSC maintenance and ferroptosis evasion in OSCC. Targeting KIF20A, either as a monotherapy or in combination with chemotherapy, may offer a promising strategy to improve therapeutic outcomes in OSCC.
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR CANCER RESEARCH
·
2024
·
IF 4.1
Yao Huihui,Xu Jiancheng,Zhou Aina,Shen Danyang,Dong Qiuchen,Yang Xiaodong,Li Mengyu,Mi Xiuwei,Lu Yang,Zhong Runze,Shi Xinyu,Tai Qingliang,Chen Guoliang,Shi Bo,Sun Liang,Zhou Diyuan,Yao Yizhou,He Songbing
Recent evidence indicates that a high-fat diet (HFD) can promote tumor development, especially colorectal cancer (CRC), by influencing the microbiota. Regulatory circular RNAs (circRNAs) play an important role in modulating host–microbe interactions; however, the specific mechanisms by which circRNAs influence cancer progression by regulating these interactions remain unclear. Here, we report that consumption of a HFD modulates the microbiota by specifically upregulating the expression of the noncoding RNA hsa_circ_0126925 (herein referred to as circ_0126925) in CRC. Acting as a scaffold, circ_0126925 hinders the recruitment of the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21) to branched-chain amino acid transaminase 2 (BCAT2), leading to reduced degradation of BCAT2. This reduction in targeted degradation of BCAT2 can protect tumours from limited branched-chain amino acids (BCAAs) interference by improving the metabolism of BCAAs in CRC. Taken together, these data demonstrate that circ_0126925 plays a critical role in promoting the progression of CRC by maintaining BCAA metabolism and provide insight into the functions and crosstalk of circ_0126925 in host–microbe interactions in CRC.
Implications: This study preliminarily confirms that circRNAs do indeed respond to microbiota/microbial metabolites, providing further evidence for the potential development of circRNAs as diagnostic tools and/or therapeutic agents to alleviate microbiome related pathology in humans.
研究领域:
肿瘤学
·
微生物学
·
分子生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）