Deacetylation of Notch1 by SIRT1 contributes to HBsAg- and HBeAg-mediated M2 macrophage polarization

Li, Jiahui; Yu, Mengxue; Zong, Ruobin; Fan, Chengpeng; Ren, Fu; Wu, Wei; Li, Changyong

doi:10.1152/ajpgi.00338.2021

Cited by 10 publications

(9 citation statements)

References 46 publications

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“…Therefore, targeting the activation of SIRT1 has become a promising strategy for treating PMOP (Kim et al, 2017). SIRT1 acts as a negative modulator of Notch1 signaling, inhibiting the Notch1 signal by promoting the deacetylation of NICD (Collesi et al, 2018; Li et al, 2022). In this study, we also established that the expression of SIRT1 was significantly downregulated in BMSCs or bone tissue of OVX rats, which SB could significantly up‐regulate.…”

Section: Discussionmentioning

confidence: 99%

SIRT1/Notch1 signal axis involves in the promoting effect of Segetalin B on bone formation

Lan

Cheng

et al. 2022

Drug Development Research

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Phytoestrogens are a class of potential natural medicines for treating postmenopausal osteoporosis (PMOP). Segetalin B (SB) is a cyclic peptide compound showing estrogenic activity. This study reports the effect of SB on bone formation among ovariectomized (OVX) rats. The bone marrow mesenchymal stem cells (BMSCs) from OVX rats were cultured in vitro. Alizarin Red staining was utilized to observe the effect of SB on the mineralization of BMSCs. The levels of alkaline phosphatase (ALP), osteocalcin, bone morphogenetic protein (BMP‐2), and Sirtuin 1 (SIRT1) activities were detected. The OVX rats were treated with SB in vivo. Micro‐CT was utilized for imaging analysis. Urine calcium and phosphorus, and ALP activity in bone marrow were assayed. Western blot analysis and immunofluorescence were incorporated to detect protein expressions in vitro and in vivo. The results showed that SB dose‐dependently promoted mineralization of OVX rat‐derived BMSCs in vitro increased the level of Osteocalcin, BMP‐2, ALP, and SIRT1 activity. Moreover, it upregulated expressions of Runx2, Osterix, and SIRT1, downregulated expressions of Notch intracellular domain (NICD), acetyl‐NICD, and hairy and enhancer of split 1 (Hes1). In addition, SB treatment significantly decreased bone loss, inhibited calcium and phosphorus loss, elevated ALP activity, upregulated Runx2, Osterix, and SIRT1, and downregulated NICD and Hes1 in OVX rats in vivo. However, EX527, a SIRT1‐selective inhibitor, could reverse the above effects of SB in vitro or in vivo. These results indicate that SB is a potential natural medicine to improve PMOP. Thus, its mechanism of promoting bone formation involves the SIRT1/Notch1 signaling axis.

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Section: Discussionmentioning

confidence: 99%

SIRT1/Notch1 signal axis involves in the promoting effect of Segetalin B on bone formation

Lan

Cheng

et al. 2022

Drug Development Research

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“…Several studies showed the most indicative biomarkers were involved in anti-HBV infection immunotherapy. Secretion of HBsAg and HBeAg promoted macrophage polarization from M1 phenotype towards M2 via the SIRT1/Notch1 pathway ( 30 ). Inhibitory receptor programmed death receptor 1 (PD-1) which contributes to T cell exhaustion was well-tolerated in chronic hepatitis B virus infection (CHB) HBeAg-negative patients, which caused HBsAg decline in most CHB patients ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Machine learning-based predictive and risk analysis using real-world data with blood biomarkers for hepatitis B patients in the malignant progression of hepatocellular carcinoma

et al. 2022

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Hepatitis B Virus (HBV) infection may lead to various liver diseases such as cirrhosis, end-stage liver complications, and Hepatocellular carcinoma (HCC). Patients with existing cirrhosis or severe fibrosis have an increased chance of developing HCC. Consequently, lifetime observation is currently advised. This study gathered real-world electronic health record (EHR) data from the China Registry of Hepatitis B (CR-HepB) database. A collection of 396 patients with HBV infection at different stages were obtained, including 1) patients with a sustained virological response (SVR), 2) patients with HBV chronic infection and without further development, 3) patients with cirrhosis, and 4) patients with HCC. Each patient has been monitored periodically, yielding multiple visit records, each is described using forty blood biomarkers. These records can be utilized to train predictive models. Specifically, we develop three machine learning (ML)-based models for three learning tasks, including 1) an SVR risk model for HBV patients via a survival analysis model, 2) a risk model to encode the progression from HBV, cirrhosis and HCC using dimension reduction and clustering techniques, and 3) a classifier to detect HCC using the visit records with high accuracy (over 95%). Our study shows the potential of offering a comprehensive understanding of HBV progression via predictive analysis and identifies the most indicative blood biomarkers, which may serve as biomarkers that can be used for immunotherapy.

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“…Notably, accumulating evidence demonstrates that liver macrophages play a double-faced role in HBV infection and pathogenesis. Indeed, on one hand M1 macrophages are known to favor HBV clearance by direct antiviral effect and by producing cytokines with trans-activating effect on adaptive immunity, on the other hand M2 macrophages and their phenotype modulation by HBV has been recently demonstrated to favor viral persistence and its related immunopathogenesis ( 95 – 97 ). Furthermore, according to literature, M1 macrophages suppresses early HCC tumorigenesis by eliminating cancer cells while M2 macrophages promote cancer cells proliferation and invasion by suppressing the adaptive immune system.…”

Section: Potential Implications Of Hbv Lymphotropism For Antiviral Tr...mentioning

confidence: 99%

New insights into hepatitis B virus lymphotropism: Implications for HBV-related lymphomagenesis

Svicher

Salpini²,

D’Anna³

et al. 2023

Front. Oncol.

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HBV is one of the most widespread hepatitis viruses worldwide, and a correlation between chronic infection and liver cancer has been clearly reported. The carcinogenic capacity of HBV has been reported for other solid tumors, but the largest number of studies focus on its possible lymphomagenic role. To update the correlation between HBV infection and the occurrence of lymphatic or hematologic malignancies, the most recent evidence from epidemiological and in vitro studies has been reported. In the context of hematological malignancies, the strongest epidemiological correlations are with the emergence of lymphomas, in particular non-Hodgkin’s lymphoma (NHL) (HR 2.10 [95% CI 1.34-3.31], p=0.001) and, more specifically, all NHL B subtypes (HR 2.14 [95% CI 1.61-2.07], p<0.001). Questionable and unconfirmed associations are reported between HBV and NHL T subtypes (HR 1.11 [95% CI 0.88-1.40], p=0.40) and leukemia. The presence of HBV DNA in peripheral blood mononuclear cells has been reported by numerous studies, and its integration in the exonic regions of some genes is considered a possible source of carcinogenesis. Some in vitro studies have shown the ability of HBV to infect, albeit not productively, both lymphomonocytes and bone marrow stem cells, whose differentiation is halted by the virus. As demonstrated in animal models, HBV infection of blood cells and the persistence of HBV DNA in peripheral lymphomonocytes and bone marrow stem cells suggests that these cellular compartments may act as HBV reservoirs, allowing replication to resume later in the immunocompromised patients (such as liver transplant recipients) or in subjects discontinuing effective antiviral therapy. The pathogenetic mechanisms at the basis of HBV carcinogenic potential are not known, and more in-depth studies are needed, considering that a clear correlation between chronic HBV infection and hematological malignancies could benefit both antiviral drugs and vaccines.

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Deacetylation of Notch1 by SIRT1 contributes to HBsAg- and HBeAg-mediated M2 macrophage polarization

Cited by 10 publications

References 46 publications

SIRT1/Notch1 signal axis involves in the promoting effect of Segetalin B on bone formation

SIRT1/Notch1 signal axis involves in the promoting effect of Segetalin B on bone formation

Machine learning-based predictive and risk analysis using real-world data with blood biomarkers for hepatitis B patients in the malignant progression of hepatocellular carcinoma

New insights into hepatitis B virus lymphotropism: Implications for HBV-related lymphomagenesis

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