Aspartate (Asp) can act on liver Kupffer cells, inhibit NOD-like receptor-P 3 (NLRP3) inflammatory bodies, and improve liver inflammation in acute hepatitis. However, the effect of Asp on the role of hepatic stellate cells (HSCs) in the pathogenesis of liver fibrosis in chronic liver injury remains unexplored. This study aimed to investigate the effects of Asp on CCl4‑induced liver fibrosis in mice and HSCs via the NF-κB/ NLRP3 signaling pathway. Liver fibrosis was induced in C57BL/6J mice by intraperitoneally (IP) injecting 0.5 mL/kg 2% CCl4 three times weekly for 8 weeks. Asp was administered to mice by gavage once every morning for 4 weeks. Masson's trichrome staining, Sirius red staining and hematoxylin and eosin staining were used to detect and analyze the pathological changes in liver tissues. Western blot analysis and immunohistochemistry were applied to determine the protein expression levels of α‑smooth muscle actin (α‑SMA), collagen Ⅲ (COL Ⅲ), NLRP3, and IL-1β. Also, reverse transcription‑quantitative PCR was performed to detect the mRNA expression levels. In the liver fibrosis model, the pathological changes in liver tissues improved following treatment with Asp. A marked decrease was observed in protein and mRNA expression levels of α‑SMA, COL Ⅲ, NLRP3, and IL-1β. In addition, HSCs were treated with Asp. The expression levels of α‑SMA, COL Ⅲ, NLRP3, and IL-1β reduced in dose‑ and time-dependent manners. Furthermore, Asp upregulated the expression of NS3TP1 in vivo and in vitro, and NS3TP1 had a significant inhibitory effect on liver fibrosis. Asp attenuated liver fibrosis and reduced collagen production by suppressing the NF-κB/ NLRP3 signaling pathway via upregulating the expression of NS3TP1.
Tenofovir disoproxil fumarate (TDF) seems to prevent hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV). However, the mechanism is still little known. This study aimed to investigate the the roles and mechanisms of TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) on the malignant characteristics of liver cancer cells. Using the wound-healing assays, transwell assays, matrigel transwell assays, and cell counting kit-8 (CCK-8) assays, it was possible to identify that TDF/TAF, inhibited migration, invasion, and proliferation of HepG2 cells and Huh7 cells. To investigate the mechanisms, we performed TOP/FOP-Flash system, Western blot, and RT-qPCR assays of liver cancer cells cultured with TDF/TAF and found a lower activity of Wnt/β-catenin signaling pathway compared with control cells. Finally, Hepatitis C virus p7 trans-regulated protein 3 (P7TP3), a tumor suppressor in HCC, was significantly increased in HepG2 cells and Huh7 cells that treated with TDF/TAF. However, entecavir (ETV)-treated liver cancer cells showed no significant difference in the malignant characteristics of HCC cells, activity of Wnt/β-catenin signaling pathway, and expression of p7TP3, compared with the control groups. To conclude, TDF/TAF maybe novel promising therapeutic strategy for HCC via Wnt/β-catenin signaling pathway, by up-regulating expression of the tumor suppressor, P7TP3.
The situation of liver fibrosis is still serious, but there is no effective treatment at present. Therefore, additional study on the mechanism of liver fibrosis is an urgent requirement. The present study aimed to elucidate the mechanism of NS3TP1 in liver fibrosis and the regulatory role of NS3TP1-SEP and calcitriol on NS3TP1. All experiments were performed in LX-2 cell lines and CCl4-induced C57BL/6 wild-type mice liver. NS3TP1 promoted differentiation, activation, and proliferation of hepatic stellate cells (HSCs) and upregulated liver fibrosis through TGFβ1/Smad3 and NF-κB signaling pathways. Both Smad3 and p65 bind to NS3TP1, and p65 upregulated the promoter of NS3TP1, while NS3TP1 upregulated the promoter of TGFβRI. ASDURF regulated the expression of NS3TP1. After overexpression of ASDURF, NS3TP1 and liver fibrosis-related genes were upregulated, whereas after interference, NS3TP1 and liver fibrosis-related genes were downregulated, besides, ASDURF and NS3TP1 had a binding effect and upregulated the promoter of NS3TP1. Calcitriol significantly inhibited CCl4-induced liver fibrosis in mice and regulated the differentiation, activation, and proliferation of HSCs. Furthermore, calcitriol regulated the activities of TGFβ1/Smad3 and NF-κB/NLRP3 inflammasome signaling pathways via downregulation of NS3TP1. These findings provided evidence for the role of NS3TP1 as a new promising therapeutic target in liver fibrosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.