Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells

Wang, Xiuling; Liu, Zhongchun; Wang, Peigang; Li, Shan; Zeng, Jie; Tu, Xiaoning; Yan, Qiujin; Xiao, Zheman; Pan, Meng‐Xian; Zhu, Fan

doi:10.1016/j.bbi.2017.09.009

Cited by 50 publications

(74 citation statements)

References 35 publications

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“…Taken together with the results that CKLF1 was involved in the progression of HCC and had oncogenic potential in HCC, it was highly plausible that CKLF1 might function as a tumor promoter in the inflammation-associated carcinogenesis and tumor progression in HCC. IL6, one of the tumor-promoting cytokines, causes hepatic inflammation, positively correlates with the progression of HCC, and activates the oncogenic factor STAT3 (42)(43)(44). STAT3 is the most crucial molecules in the IL6 signaling pathway and is recognized as a pivotal link between inflammation and cancer (24)(25)(26).…”

Section: Cklf1 Is a Recently Discovered Chemokine With Broad-spectrummentioning

confidence: 99%

CKLF1 Enhances Inflammation-Mediated Carcinogenesis and Prevents Doxorubicin-Induced Apoptosis via IL6/STAT3 Signaling in HCC

Liu

Zhou

et al. 2019

Clinical Cancer Research

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Purpose: Hepatocellular carcinoma (HCC), one of the most common and deadliest malignancies worldwide, has a poor prognosis, owing to its high potential for vascular invasion and metastasis and the lack of biomarkers for early diagnosis. Thus, it must be a crucial factor for investigating therapeutic strategies for HCC to identify the functional molecular targets. Here, we reported a novel chemokine, CKLF1, that might act as a pivotal modulator in the invasion and metastasis of HCC and could serve as an attractive target for cancer therapy.Experimental Design: Bioinformatics analysis, PCR, Western blotting, and IHC were performed to detect the expression of CKLF1 in HCC. The function of CKLF1 was demonstrated by a series of in vitro and in vivo experiments. Pharmacologic treatment, flow cytometry, and Western blotting were carried out to demonstrate the potential mechanisms of CKLF1.Results: We proved that CKLF1 was overexpressed in HCC tissues and was related to tumor stage, vascular invasion, and patient survival. Then, functional assays showed that CKLF1 promoted hepatocellular carcinogenesis and metastatic potential. Finally, the IL6/STAT3 signaling pathway was involved in the mechanistic investigation. The results demonstrated that CKLF1 enhanced the progression of HCC and prevented doxorubicin-induced apoptosis through activating the IL6/ STAT3 pathway.Conclusions: These data showed that CKLF1 inhibited apoptosis and promoted malignant transformation through the IL6/STAT3 pathway, and ultimately enhanced the development and metastasis of HCC. Thus, our work revealed that CKLF1 was a significant prognostic factor of HCC and might be a potential molecular therapeutic target for HCC.

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Section: Cklf1 Is a Recently Discovered Chemokine With Broad-spectrummentioning

confidence: 99%

CKLF1 Enhances Inflammation-Mediated Carcinogenesis and Prevents Doxorubicin-Induced Apoptosis via IL6/STAT3 Signaling in HCC

Liu

Zhou

et al. 2019

Clinical Cancer Research

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“…Our previous data supported this possibility. Our study found that Syncytin-1 could trigger the production of inflammatory cytokines CRP and IL-6 in microglial and astroglial cells ( 22 ). Another study also suggested that Syncytin-1 can induce inflammation by promoting the secretion of IL-6, IL-1β, and TNF-α in human monocytes ( 90 ).…”

Section: Commentsmentioning

confidence: 75%

“…In our previous study, we identified the positive mRNA transcription of Syncytin-1 in the plasma samples of 42 in 118 patients with recent-onset schizophrenia; however, none from 106 controls was found ( 3 ). We also detected increased protein level of Syncytin-1 in the sera of 99 patients with schizophrenia relative to that of 83 normal individuals by ELISA assay ( 22 ). These results, when combined, suggest that Syncytin-1 is involved in the development of schizophrenia.…”

Section: Syncytin-1 and Neurological Diseasesmentioning

confidence: 82%

“…In our recent study, we reported that Syncytin-1 exhibited a positive correlation and marked consistency with the expression levels of CRP in individuals with schizophrenia. We also found that Syncytin-1 could trigger the activation of CRP via the TLR3-IL-6 signal pathway in glial cells, the deficiency of TLR3 could significantly impair Syncytin-1-induced CRP and IL-6 expression ( 22 ). Direct interaction and cellular colocalization between Syncytin-1 and TLR3 were observed by confocal microscopy ( 22 ).…”

Section: Syncytin-1 Could Cause Inflammatory Abnormalities In Neuropsmentioning

confidence: 93%

“…We also found that Syncytin-1 could trigger the activation of CRP via the TLR3-IL-6 signal pathway in glial cells, the deficiency of TLR3 could significantly impair Syncytin-1-induced CRP and IL-6 expression ( 22 ). Direct interaction and cellular colocalization between Syncytin-1 and TLR3 were observed by confocal microscopy ( 22 ). Thus, TLR3 can potentially function as a Syncytin-1 mediator to induce inflammatory abnormalities in the glial cell.…”

Section: Syncytin-1 Could Cause Inflammatory Abnormalities In Neuropsmentioning

confidence: 93%

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Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases

2018

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Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome. Recent studies have considered HERVs as potential pathogenic factors. The majority of HERV genes are mutated and not capable of encoding functional proteins; regardless, some HERV genes, such as HERV-W envelope (env) glycoprotein, are known to have intact open reading frames. The HERV-W element on 7q21.2, which encodes a protein referred to as Syncytin-1, participates in human placental morphogenesis and can activate a pro-inflammatory and autoimmune cascade. Neuropsychological disorders are typically linked to inflammatory abnormalities. In this study, we review that Syncytin-1 has been increasingly involved in the development of neuropsychological disorders, such as schizophrenia and multiple sclerosis (MS). This study also presents inflammation imbalances in schizophrenia and MS. More importantly, we discuss the potential role and molecular mechanisms by which Syncytin-1 regulates inflammatory abnormalities in neuropsychological diseases. In summary, Syncytin-1 activity may represent a novel molecular pathogenic mechanism in neuropyschological diseases, such as schizophrenia and MS.

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Neuronal C‐Reactive Protein/FcγRI Positive Feedback Proinflammatory Signaling Contributes to Nerve Injury Induced Neuropathic Pain

Liu

Zhang

et al. 2023

Advanced Science

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Neuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that the neuronal Fc‐gamma‐receptor type I (FcγRI) of the dorsal root ganglion (DRG) mediates antigen‐specific pain. However, the mechanisms of neuronal FcγRI in neuropathic pain remain to be explored. Here, it is found that the activation of FcγRI‐related signals in primary neurons induces neuropathic pain in a rat model. This work first reveals that sciatic nerve injury persistently activates neuronal FcγRI‐related signaling in the DRG, and conditional knockout (CKO) of the FcγRI‐encoding gene Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after nerve injury. C‐reactive protein (CRP) is increased in the DRG after nerve injury, and CRP protein of the DRG evokes pain by activating neuronal FcγRI‐related signals. Furthermore, microinjection of naive IgG into the DRG alleviates neuropathic pain by suppressing the activation of neuronal FcγRI. These results indicate that the activation of neuronal CRP/FcγRI‐related signaling plays an important role in the development of neuropathic pain in chronic constriction injury (CCI) rats. The findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and suggest potential therapeutic targets for neuropathic pain.

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Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells

Cited by 50 publications

References 35 publications

CKLF1 Enhances Inflammation-Mediated Carcinogenesis and Prevents Doxorubicin-Induced Apoptosis via IL6/STAT3 Signaling in HCC

CKLF1 Enhances Inflammation-Mediated Carcinogenesis and Prevents Doxorubicin-Induced Apoptosis via IL6/STAT3 Signaling in HCC

Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases

Neuronal C‐Reactive Protein/FcγRI Positive Feedback Proinflammatory Signaling Contributes to Nerve Injury Induced Neuropathic Pain

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