scholarly journals Correlation of Interleukin-33/ST2 Receptor and Liver Fibrosis Progression in Biliary Atresia Patients

2019 ◽  
Vol 7 ◽  
Author(s):  
Jia Liu ◽  
YiFan Yang ◽  
Chao Zheng ◽  
Gong Chen ◽  
Zhen Shen ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Interleukin 33 ◽  
Fibrosis Progression ◽  
St2 Receptor

Could interleukin-33 and its suppressor of tumorigenicity 2 (ST2) receptor have a role in cervical human papillomavirus (HPV) infections?

2019 ◽  
Vol 35 (9) ◽  
pp. 796-802
Author(s):  
Nur Gozde Kulhan ◽  
Mehmet Kulhan ◽  
Merve Aydin ◽  
Umit Nayki ◽  
Cenk Nayki ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Interleukin 33 ◽  
St2 Receptor ◽  
Cervical Human Papillomavirus

scholarly journals Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

2020 ◽  
Vol 7 ◽  
Author(s):  
Mark Nomden ◽  
Leonie Beljaars ◽  
Henkjan J. Verkade ◽  
Jan B. F. Hulscher ◽  
Peter Olinga
Keyword(s):  
Immune Response ◽  
Liver Fibrosis ◽  
Pulmonary Fibrosis ◽  
Matrix Metalloproteinase ◽  
Biliary Atresia ◽  
Adaptive Immune Response ◽  
Cell Contact ◽  
T Helper 1 ◽  
Matrix Metalloproteinase 7

Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

scholarly journals Increased MMP‐7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia

2016 ◽  
Vol 2 (3) ◽  
pp. 187-198 ◽  
Author(s):  
Anna Kerola ◽  
Hanna Lampela ◽  
Jouko Lohi ◽  
Päivi Heikkilä ◽  
Annika Mutanen ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Biliary Epithelium ◽  
Native Liver

scholarly journals YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Zheng ◽  
Jiaqian Luo ◽  
Yifan Yang ◽  
Rui Dong ◽  
Fa-Xing Yu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Biliary Atresia ◽  
Signaling Pathway ◽  
Target Genes ◽  
Hippo Signaling ◽  
Mice Model ◽  
Hippo Signaling Pathway ◽  
Ductal Cells

Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model.Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status.Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model.Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.

scholarly journals Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Song Sun ◽  
Menghua Xu ◽  
Peijun Zhuang ◽  
Gong Chen ◽  
Kuiran Dong ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Transforming Growth Factor ◽  
Serum Vitamin ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Control Group ◽  
Serum Vitamin D ◽  
Duct Ligation ◽  
Tgf Β1

AbstractTo investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.

scholarly journals Identification of GDF15 as A Pro-Fibrotic Factor in Mouse Liver Fibrosis Progression

2021 ◽  
Author(s):  
Peng Qi ◽  
Ming-Ze Ma ◽  
Jing-Hua Kuai
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Liver Tissue ◽  
Cell Activation ◽  
Stellate Cell ◽  
Neutralizing Antibody ◽  
Stellate Cells ◽  
Fibrosis Progression

Abstract Aim:To elucidate the inhibitory role of growth differentiation factor 15 (GDF15) in liver fibrosis and its possible activation mechanism in hepatic stellate cells of mice.Methods:We generated a GDF15-neutralizing antibody that can inhibit TGF-β1-induced activation of the TGF-β/Smad2/3 pathway in LX-2 cells. All the mice in this study were induced by carbon tetrachloride and thioacetamide. In addition, primary hepatic stellate cells from mice were isolated from fresh livers using Nycodenz density gradient separation. The severity and extent of liver fibrosis in mice were evaluated by Sirius Red and Masson staining. The effect of GDF15 on the activation of the TGF-β pathway was detected using dual-luciferase reporter assays and Western blotting assays.Results:The expression of GDF15 in cirrhotic liver tissue was higher than that in normal liver tissue. Blocking GDF15 with a neutralizing antibody resulted in a delay in primary hepatic stellate cell activation and remission of liver fibrosis induced by carbon tetrachloride or thioacetamide. Meanwhile, TGF-β pathway activation was partly inhibited by a GDF15-neutralizing antibody in primary hepatic stellate cells. These results indicated that GDF15 plays an important role in regulating HSC activation and liver fibrosis progression.Conclusions:The inhibition of GDF15 attenuates chemical-inducible liver fibrosis and delays hepatic stellate cell activation, and this effect is probably mainly attributed to its regulatory role in TGF-β signalling.

Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Emanuele Angelucci ◽  
Pietro Muretto ◽  
Antonio Nicolucci ◽  
Donatella Baronciani ◽  
Buket Erer ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Iron Overload ◽  
Iron Content ◽  
Hazard Rate ◽  
Iron Concentration ◽  
Dry Weight ◽  
Interquartile Range ◽  
Hepatic Iron ◽  
Fibrosis Progression

Abstract To identify the role of iron overload in the natural history of liver fibrosis, we reviewed serial hepatic biopsy specimens taken annually from patients cured of thalassemia major by bone marrow transplantation. The patients underwent transplantation between 1983 and 1989 and did not receive any chelation or antiviral therapy. Two hundred eleven patients (mean age, 8.7 ± 4 years) were evaluated for a median follow-up of 64 months (interquartile range, 43-98 months) by a median number of 5 (interquartile range, 3-6) biopsy samples per patient. Hepatic iron concentration was stratified by tertiles (lower, 0.5-5.6 mg/g; medium, 5.7-12.7 mg/g; upper, 12.8-40.6 mg/g dry weight). Forty-six (22%) patients showed signs of liver fibrosis progression; the median time to progression was 51 months (interquartile range, 36-83 months). In a multivariate Cox proportional hazard model, the risk for fibrosis progression correlated to medium hepatic iron content (hazard rate, 1.9; 95% confidence interval [CI], 0.74-5.0), high hepatic iron content (hazard rate, 8.7; 95% CI, 3.6-21.0) and hepatitis C virus (HCV) infection (hazard rate, 3.1; 95% CI, 1.5-6.5). A striking increase in the risk for progression was found in the presence of both risk factors. None of the HCV-negative patients with hepatic iron content lower than 16 mg/g dry weight showed fibrosis progression, whereas all the HCV-positive patients with hepatic iron concentration greater than 22 mg/g dry weight had fibrosis progression in a minimum follow-up of 4 years. Thus, iron overload and HCV infection are independent risk factors for liver fibrosis progression, and their concomitant presence results in a striking increase in risk.

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