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Liver sinusoidal endothelial cells (LSECs) locate on the surface of hepatic sinusoids. As the first line of defense between the liver and blood, LSECs are the most abundant non-parenchymal cells in the liver. Under physiological conditions, LSECs may induce liver immune tolerance through participating in substance transport and metabolic waste removal, thereby maintaining liver homeostasis, and under pathological conditions, LSECs may promote liver immune response via antigen presentation. LSECs have been found to play a crucial regulatory role in maintaining the balance between liver regeneration and liver fibrosis. This article reviews the progress of researches on LSECs functions, LSECs changes in liver injury, signal pathways associated with regulation of LSECs functions, and the interaction between LSECs and other types of cells in the liver, aiming to elucidate the function of LSECs and their roles in liver diseases.
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The liver has a unique immune microenvironment, and the intrinsic antigen-presenting cells in the liver interact with each other and form a network to accurately regulate the homeostasis between liver immune tolerance and immune response. During hepatitis B virus (HBV) infection, on the one hand, the intrahepatic intrinsic antigen-presenting cells induce immune tolerance to help the virus escape immune clearance and thus result in persistent infection; on the other hand, the maturation and activation of the intrahepatic intrinsic antigen-presenting cells can also mediate effective anti-HBV immune response to achieve virus clearance. This article elaborates on the research advances in the role and mechanism of action of intrahepatic intrinsic antigen-presenting cells in regulating immune response against HBV infection.
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With the increasing incidence rate of nonalcoholic fatty liver disease (NAFLD) in Western developed countries and rich regions of China year by year, the treatment methods for NAFLD have been constantly improved and NAFLD has become a research hotspot. As an important physiological structure of the liver, liver sinus endothelial cells (LSECs) play an important role in the development and progression of NAFLD. This article summarizes the mechanism of action of LSECs in the pathogenesis of NAFLD, which included the following aspects: LSEC capillarization occurs in nonalcoholic fatty liver and promotes steatosis; meanwhile, LSECs contribute to oxidative stress in nonalcoholic steatohepatitis (NASH) and is a major effector of liver inflammation in NASH, thus promoting liver fibrosis; in addition, angiogenesis is highly stimulated and promotes NAFLD-related hepatocellular carcinoma in NAFLD. However, the role of LSECs in NASH-associated liver cirrhosis has not been validated, which needs to be further clarified to provide new ideas and directions for treatment.
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Objective To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS)in the treatment of patients with hepatic sinusoidal obstruction syndrome (HSOS).Methods From April 2015 to August 2018,at The First Affiliated Hospital of University of Science and Technology of China,21 patients with gynura segetum caused HSOS were selected.All the patients received TIPS treatment because of unresponsiveness to anticoagulant therapy for at least two weeks.After operation patients were followed up with liver and portal vein Doppler ultrasonography examination,liver and kidney function tests,and survival observation.T test,logistic univariate regression analysis and Cox regression analysis were performed for statistical analysis.Results Among the 21 patients with gynura segetum-related HSOS,18 patients were in the subacute phase and three patients in the chronic phase.All of them were moderate or severe patients and all successfully underwent TIPS.The postoperative portal vein pressure was (16.71 ± 4.68) cmH2O (1 cmH2O =0.098 kPa),which was lower than that before operation ((41.52 ±6.27) cmH2O),and the difference was statistically significant (t =16.936,P ＜ 0.01).The postoperation portal vein blood flow velocity was (41.52 ±7.70) cm/s,which was higher than before operation ((11.19 ± 3.29) cm/s),and the difference was statistically significant (t =-15.191,P ＜0.01).At one month after operation,15 of 21 patients were clinically cured;among the remaining six patients,four patients were improved and two patients were ineffective (including one patient died).At four months after operation,two patients died,and the remaining 19 patients were clinically cured.At one month after operation,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBil) and serum creatinine were (23.7 ± 16.8) U/L,(33.9 ±7.4) U/L,(52.7 ± 38.2) μmol/L and (62.7 ± 12.6) μmol/L,respectively,which were lower than those before operation ((60.5 ± 42.4) U/L,(78.4 ± 42.4) U/L,(74.9 ± 38.2) μmol/L and (82.4 ± 19.6) μmol/L,respectively),and the differences were statistically significant (t =3.193,3.493,2.378 and 4.519;all P ＜ 0.05).The level of albumin was (39.0 ±3.1) g/L,which was higher than that before operation ((30.9 ± 3.8) g/L),and the difference was statistically significant (t =-10.283,P ＜ 0.01).Portal vein thrombosis and preoperative TBil level had predictive value for therapeutic efficacy (both P ＜0.05).The one-year cumulative survival rate of patients was 90.5％.Preoperative TBil level and hepatic encephalopathy had effects on the prognosis of patients (both P ＜ 0.05).Conclusion TIPS is a safe,reliable and effective treatment for patients with subacute and chronic gynura segetum-related HSOS who are not responding to ineffective anticoagulant therapy,which can improve the prognosis and survival rate of the patients.
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<p><b>OBJECTIVE</b>To study the effects of Astragalus polysaccharide (APS), the primary effective component of the Chinese herb medicine Astragalus membranaceus (frequently used for its anti-hepatic fibrosis effects), on nanoscale mechanical properties of liver sinusoidal endothelial cells (SECs).</p><p><b>METHODS</b>Using endothelial cell medium as the control, 5 experimental groups were established utilizing different concentrations of APS, i.e. 12.5, 25, 50, 100, and 200 μg/mL. By using atomic force microscopy along with a microcantilever modified with a silicon dioxide microsphere as powerful tools, the value of Young's modulus in each group was calculated. SAS 9.1 software was applied to analyze the values of Young's modulus at the pressed depth of 300 nm. Environmental scanning electron microscopy was performed to observe the surface microtopography of the SECs.</p><p><b>RESULTS</b>The value of Young's modulus in each APS experimental group was significantly greater than that of the control group: as APS concentration increased, the value of Young's modulus presented as an increasing trend. The difference between the low-concentration (12.5 and 25 μg/mL) and high-concentration (200 μg/mL) groups was statistically significant (P<0.05), but no significant differences were observed between moderateconcentration (50 and 100 μg/mL) groups versus low- or high-concentration groups (P>0.05). Surface topography demonstrated that APS was capable of increasing the total area of fenestrae.</p><p><b>CONCLUSIONS</b>The values of Young's modulus increased along with increasing concentrations of APS, suggesting that the stiffness of SECs increases gradually as a function of APS concentration. The observed changes in SEC mechanical properties may provide a new avenue for mechanistic research of anti-hepatic fibrosis treatments in Chinese medicine.</p>
Subject(s)
Animals , Rats , Astragalus Plant , Chemistry , Biomechanical Phenomena , Elastic Modulus , Endothelial Cells , Cell Biology , Liver , Cell Biology , Microscopy, Atomic Force , Microspheres , Nanotechnology , Polysaccharides , Pharmacology , Silicon Dioxide , Chemistry , Surface PropertiesABSTRACT
To investigate the effects of cryptotanshinone (an active ingredient of Salvia Miltiorrhiza) inhibition of angiogenesis, the toxicity of cryptotanshinone was assayed in human hepatic sinusoidal endothelial cells (HHSEC) by CCK8 method. Max dose without toxicity is 10 μmol·L-1. The proliferation of HHSEC were induced by the endothelial cell growth supplement (ECGS), with 2.5 μmol·L-1 sorafenib as the positive control. Cell proliferation was analyzed by EdU assay. Cell viability was analyzed by CCK8 method. The expression of vWF was analyzed by immunofluorescence method. Fluorescence probe method was used to detect the intracellular nitric oxide (NO) levels. Tube formation of HHSEC and transgenic zebrafish were also observed to evaluate the effects of cryptotanshinone against angiogenesis. Compared with normal control, there is a proliferation of HHSEC induced by ECGS. The expression of vWF and the NO levels increased significantly. Cryptotanshinone inhibited the proliferation, down regulated the expression of vWF and the NO levels. Further, cryptotanshinone inhibited the tube formation of HHSEC and reduced the number of fu nctional vessels in transgenic zebrafish. The results suggest that cryptotanshinone could inhibit angiogenesis by regulating the HHSEC cell function.
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The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions.