Cyclophilin A causes severe fever with thrombocytopenia syndrome virus-induced cytokine storm by regulating mitogen-activated protein kinase pathway

Huang, Huaying; Jin, Ke; OuYang, Ke; Jiang, Zhengyi; Zhan, Yang; Hu, Nannan; Dai, Yan; Zhang, Yaqin; Zhang, Qian; Han, Ying; Zhao, Jie; Lin, Hong; Wang, Chunhui; Wang, Chunyan; Sun, Xuewei; Lu, Da-Feng; Zhu, Jin; Li, Jun

doi:10.3389/fmicb.2022.1046176

Cited by 6 publications

(2 citation statements)

References 44 publications

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“…Consistent with the in vitro experiments, AC-73 treatment attenuated the increase in xenograft tumor volume and weight induced by TIE1 overexpression (Figure 5 F-H). It has been reported that AC-73 could specifically disrupt Basigin dimerization, thereby suppressing the Basigin/ERK1/2/MMPs pathways 23 , 24 . So, we conducted a Western blotting experiment, confirming that TIE1 can activate MAPK/ERK pathway in cervical cancer cells ( Figure S8 ).…”

Section: Resultsmentioning

confidence: 99%

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis

Liu,

Xie,

et al. 2024

Int. J. Biol. Sci.

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Background: Tyrosine kinase with immunoglobulin and EGF-like domains 1 (TIE1) is known as an orphan receptor prominently expressed in endothelial cells and participates in angiogenesis by regulating TIE2 activity. Our previous study demonstrated elevated TIE1 expression in cervical cancer cells. However, the role of TIE1 in cervical cancer progression, metastasis and treatment remains elusive. Methods: Immunohistochemistry staining for TIE1 and Basigin was performed in 135 human cervical cancer tissues. Overexpressing vectors and siRNAs were used to manipulate gene expression in tumor cells. Colony formation, wound healing, and transwell assays were used to assess cervical cancer cell proliferation and migration in vitro. Subcutaneous xenograft tumor and lung metastasis mouse models were established to examine tumor growth and metastasis. Co-Immunoprecipitation and Mass Spectrometry were applied to explore the proteins binding to TIE1. Immunoprecipitation and immunofluorescence staining were used to verify the interaction between TIE1 and Basigin. Cycloheximide chase assay and MG132 treatment were conducted to analyze protein stability. Results: High TIE1 expression was associated with poor survival in cervical cancer patients. TIE1 overexpression promoted the proliferation, migration and invasion of cervical cancer cells in vitro, as well as tumor growth and metastasis in vivo. In addition, Basigin, a transmembrane glycoprotein, was identified as a TIE1 binding protein, suggesting a pivotal role in matrix metalloproteinase regulation, angiogenesis, cell adhesion, and immune responses. Knockdown of Basigin or treatment with the Basigin inhibitor AC-73 reversed the tumor-promoting effect of TIE1 in vitro and in vivo. Furthermore, we found that TIE1 was able to interact with and stabilize the Basigin protein and stimulate the Basigin-matrix metalloproteinase axis. Conclusion: TIE1 expression in cervical cells exerts a tumor-promoting effect, which is at least in part dependent on its interaction with Basigin. These findings have revealed a TIE2-independent mechanism of TIE1, which may provide a new biomarker for cervical cancer progression, and a potential therapeutic target for the treatment of cervical cancer patients.

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Section: Resultsmentioning

confidence: 99%

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis

Liu,

Xie,

et al. 2024

Int. J. Biol. Sci.

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“…From a histopathological standpoint, the spleen, liver, and kidney exhibit lesions upon SFTSV infection [ 44 ]. Infiltration of inflammatory cells and necrotic lesions are observed in the liver.…”

Section: Discussionmentioning

confidence: 99%

Difference in Intraspecies Transmissibility of Severe Fever with Thrombocytopenia Syndrome Virus Depending on Abrogating Type 1 Interferon Signaling in Mice

Oh,

Park,

Yang

et al. 2024

Viruses

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Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks.

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A Novel Engineering Cell Therapy Platform Mimicking the Immune Thrombocytopenia‐Derived Platelets to Inhibit Cytokine Storm in Hemophagocytic Lymphohistiocytosis

Liu,

Du,

Zhou

et al. 2024

Advanced Science

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Hemophagocytic lymphohistiocytosis (HLH) is a common and highly fatal hyperinflammatory syndrome characterized by the aberrant activation of macrophages. To date, there is a lack of targeted therapies for HLH. It is validated that macrophages in HLH efficiently phagocytose anti‐CD41‐platelets (anti‐CD41‐PLTs) from immune thrombocytopenia (ITP) patients in previous research. Hence, the pathological mechanisms of ITP are mimicked and anti‐CD41‐PLTs are utilized to load the macrophage‐toxic drug VP16 to construct macrophage‐targetable engineered platelets anti‐CD41‐PLT‐VP16, which is a novel targeted therapy against HLH. Both in vitro and in vivo studies demonstrate that anti‐CD41‐PLT‐VP16 has excellent targeting and pro‐macrophage apoptotic effects. In HLH model mice, anti‐CD41‐PLT‐VP16 prevents hemophagocytosis and inhibits the cytokine storm. Mechanistic studies reveal that anti‐CD41‐PLT‐VP16 increases the cytotoxicity of VP16, facilitating precise intervention in macrophages. Furthermore, it operates as a strategic “besieger” in diminishing hyperinflammation syndrome, which can indirectly prevent the abnormal activation of T cells and NK cells and reduce the Ab‐dependent cell‐mediated cytotoxicity effect. The first platelet‐based clinical trial is ongoing. The results show that after treatment with anti‐CD41‐PLT‐VP16, HLH patients have a threefold increase in the overall response rate compared to patients receiving conventional chemotherapy. In conclusion, anti‐CD41‐PLT‐VP16 provides a general insight into hyperinflammation syndrome and offers a novel clinical therapeutic strategy for HLH.

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Cyclophilin A causes severe fever with thrombocytopenia syndrome virus-induced cytokine storm by regulating mitogen-activated protein kinase pathway

Cited by 6 publications

References 44 publications

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis

Difference in Intraspecies Transmissibility of Severe Fever with Thrombocytopenia Syndrome Virus Depending on Abrogating Type 1 Interferon Signaling in Mice

A Novel Engineering Cell Therapy Platform Mimicking the Immune Thrombocytopenia‐Derived Platelets to Inhibit Cytokine Storm in Hemophagocytic Lymphohistiocytosis

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