Plasminogen Activator Inhibitor-1 and Oncogenesis in the Liver Disease

Nam, Da‐Eun; Seong, Hae Chang; Hahn, Young S.

doi:10.33696/signaling.2.054

Cited by 2 publications

(2 citation statements)

References 42 publications

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“…Serpin E1 has three distinct conformational states that are determined by the state of its reactive center loop (RCL) state: a metastable active form with an intact RCL exposed at the molecule surface, capable of binding to and inhibiting uPA/tPA activity; a stable latent form with an internalized and intact RCL within the protein core; and a cleaved form with a disrupted RCL [ 33 ]. Based on its structure characteristics, Serpin E1 interacts with uPA/tPA, vitronectin, and lipoprotein receptor through distinct domains [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori-induced fibroblast-derived Serpin E1 promotes gastric cancer growth and peritoneal dissemination through p38 MAPK/VEGFA-mediated angiogenesis

Cheng,

Liao,

Xie

et al. 2023

Cancer Cell Int

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Background Fibroblasts, especially cancer-associated fibroblasts (CAFs), represent the predominant stromal cell population in the tumor microenvironment and have an important function in tumorigenesis by interacting with tumor cells. However, their interaction remains elusive in an inflammatory tumor microenvironment induced by Helicobacter pylori (H. pylori). Methods The expression of Serpin family E member 1 (Serpin E1) was measured in fibroblasts with or without H. pylori infection, and primary gastric cancer (GC) cells. Serpin E1 knockdown and overexpression fibroblasts were generated using Serpin E1 siRNA or lentivirus carrying Serpin E1. Co-culture models of fibroblasts and GC cells or human umbilical vein endothelial cells (HUVECs) were established with direct contact or the Transwell system. In vitro functional experiments and in vivo tumorigenesis assay were employed to study the malignant behaviors of GC cells interacting with fibroblasts. ELISA was used for quantifying the levels of Serpin E1 and VEGFA in the culture supernatant. The tube formation capacity of HUVECs was assessed using a tube formation assay. Recombinant human Serpin E1 (recSerpin E1), anti-Serpin E1 antibody, and a MAPK pathway inhibitor were utilized to treat HUVECs for elucidating the underlying molecular mechanisms. Results Serpin E1 was predominantly expressed in gastric CAFs. H. pylori infection significantly enhanced the expression and secretion of Serpin E1 by CAFs. Both fibroblast-derived Serpin E1 and recSerpin E1 enhanced the growth, invasion, and migration of GC cells, along with increased VEGFA expression and tube formation in HUVECs. Furthermore, the co-inoculation of GC cells and fibroblasts overexpressing Serpin E1 triggered the expression of Serpin E1 in cancer cells, which facilitated together xenograft tumor growth and peritoneal dissemination of GC cells in nude mice, with an increased expression of Ki67, Serpin E1, CD31 and/or VEGFA. These processes may be mediated by Serpin E1-induced migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs. Conclusion H. pylori infection induces Serpin E1 expression in fibroblasts, subsequently triggering its expression in GC cells through their interaction. Serpin E1 derived from these cells promotes the migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs, thereby facilitating GC growth and peritoneal metastasis. Targeting Serpin E1 signaling is a potential therapy strategy for H. pylori-induced GC.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori-induced fibroblast-derived Serpin E1 promotes gastric cancer growth and peritoneal dissemination through p38 MAPK/VEGFA-mediated angiogenesis

Cheng,

Liao,

Xie

et al. 2023

Cancer Cell Int

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“…While in other publications, hyperfibrinolysis (high PAs/PAI-1 ratio) is a common condition in hepatic cirrhosis patients and is a predictor of patient severity [15]. Hyperfibrinolysis conditions that occur due to increased PA and/or decreased PAI-1 so that the risk of bleeding will be higher in patients with hepatic cirrhosis so mortality will increase as well [16], [17], [18], [19], [20].…”

Section: Discussionmentioning

confidence: 99%

Comparison of plasminogen activator inhibitor-1 levels in chronic hepatitis B patients with hepatic cirrhosis and without hepatic cirrhosis

Hamdany

Parewangi

Saleh

et al. 2022

Open Access Maced J Med Sci

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Introduction: One of the hepatic cirrhosis manifestations is bleeding disorders. Among all the substance that plays a pivotal role in maintaining the balance between thrombosis and thrombolysis is PAI-1, synthesized by hepatocytes. The dynamics of increase and decrease of PAI-1 is a natural response to the ongoing hepatic cirrhosis, but may not be seen in non-hepatic cirrhosis. PAI-1 levels also depends on the stage of fibrosis. Several conditions may interfere with PAI-1 levels including age, body mass index, and gender Objectives: This study aims to find out the comparison of PAI-1 levels in hepatitis B patients with hepatic cirrhosis and without hepatic cirrhosis and to compare it with every stage of hepatic cirrhosis. Patients and Methods: This study is an observational analytical study with a cross-sectional approach conducted at Wahidin Sudirohusodo hospitals, Makassar. Subjects are chronic hepatitis B patients with and without hepatic cirrhosis which meet inclusion criteria. Serum PAI-1 levels were measured by using Bender MedSystems human plasminogen activator inhibitor-1 ELISA kit (BMS2033) and using the ELISA technique. Statistical analysis was performed using the Kolmogorov Smirnov normality test as well as the Mann-Whitney method. Statistical results are considered significant if the p-value <0.05. Results: The research was conducted on 60 subjects who meet inclusion criteria, consisting of 33 men and 27 women. There were 16 patients with hepatic cirrhosis. Levels of PAI-1 in hepatic cirrhosis was significantly different which lower than non-hepatic cirrhosis patient (0.43 ng/mL Vs 1.11 ng/mL, p=0.024). By staging of hepatic fibrosis, stage F2 hepatic fibrosis had the highest levels of PAI-1, in contrast with end-stage hepatic fibrosis which had the lowest levels. Conclusion: Levels of PAI-1 fluctuate through different stages of hepatic fibrosis. The significant difference in PAI-1 levels in hepatic cirrhosis and non-hepatic cirrhosis demonstrates a correlation between PAI-1 and hepatic cirrhosis Keywords: Chronic hepatitis B, Hepatic cirrhosis, Plasminogen Activator Inhibitor-1

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Plasminogen Activator Inhibitor-1 and Oncogenesis in the Liver Disease

Cited by 2 publications

References 42 publications

Helicobacter pylori-induced fibroblast-derived Serpin E1 promotes gastric cancer growth and peritoneal dissemination through p38 MAPK/VEGFA-mediated angiogenesis

Helicobacter pylori-induced fibroblast-derived Serpin E1 promotes gastric cancer growth and peritoneal dissemination through p38 MAPK/VEGFA-mediated angiogenesis

Comparison of plasminogen activator inhibitor-1 levels in chronic hepatitis B patients with hepatic cirrhosis and without hepatic cirrhosis

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