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Hepatocyte growth factor

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https://www.readbyqxmd.com/read/28817220/klk14-interactions-with-hai-1-and-hai-2-serine-protease-inhibitors-a-molecular-dynamics-and-relative-free-energy-calculations-study
#1
Christian Solís-Calero, Hernandes F Carvalho
Kallikrein 14 (KLK14) is a serine protease linked to several pathologies including prostate cancer and positively correlates with Gleason score. Though KLK14 functioning in cancer is poorly understood, it has been implicated in HGF/Met signaling, given that KLK14 proteolytically inhibits HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, thereby contributing to tumor progression. In this work, KLK14 binding to either hepatocyte growth factor activator inhibitor type-1 (HAI-1) or type-2 (HAI-2) was essayed using homology modeling, molecular dynamic simulations and free-energy calculations through MM/PBSA and MM/GBSA...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28815768/micro-vesicles-derived-from-human-wharton-s-jelly-mesenchymal-stromal-cells-mitigate-renal-ischemia-reperfusion-injury-in-rats-after-cardiac-death-renal-transplantation
#2
Xiaoqiang Wu, Tianzhong Yan, Zhiwei Wang, Xuan Wu, Guanghui Cao, Chan Zhang, Xiangyong Tian, Junpeng Wang
OBJECTIVES: The purpose of the present study was to investigate the possible therapeutic effects of the human Wharton-Jelly mesenchymal stromal cells derived micro-vesicles (hWJMSCs-MVs) on renal ischemia-reperfusion injury (IRI) after cardiac death (CD) renal transplantation in rats. METHODS: MVs were injected intravenously in rats immediately after renal transplantation. The animals were sacrificed at 24 h, 48 h, 1 and 2 weeks post-transplantation. ELISA was used to determine the von Willebrand Factor (vWF), tumore necrosis factor (TNF)-α and interleukin (IL)-10 levels in the serum...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28810822/gamma-irradiated-%C3%AE-glucan-modulates-signaling-molecular-targets-of-hepatocellular-carcinoma-in-rats
#3
Sawsan M Elsonbaty, Walid E Zahran, Fatma Sm Moawed
β-glucans are one of the most abundant forms of polysaccharides known as biological response modifiers which influence host's biological response and stimulate immune system. Accordingly, this study was initiated to evaluate irradiated β-glucan as a modulator for cellular signaling growth factors involved in the pathogenesis of hepatocellular carcinoma in rats. Hepatocellular carcinoma was induced with 20 mg diethylnitrosamine/kg BW. Rats received daily by gastric gavage 65 mg irradiated β-glucan/kg BW. It was found that treatment of rats with diethylnitrosamine induced hepatic injury and caused significant increase in liver injury markers with a concomitant significant increase in both hepatic oxidative and inflammatory indices: alpha-fetoprotein, interferon gamma, and interleukin 6 in comparison with normal and irradiated β-glucan-treated groups...
August 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28810597/dual-inhibition-of-met-and-src-kinase-activity-as-a-combined-targeting-strategy-for-colon-cancer
#4
Na Song, Xiujuan Qu, Shizhou Liu, Simeng Zhang, Jing Liu, Jinglei Qu, Huachuan Zheng, Yunpeng Liu, Xiaofang Che
Hepatocyte growth factor (HGF)/MET signaling is implicated in the development of colorectal cancer (CRC) and possesses therapeutic value for various types of cancer. However, inhibition of MET alone has been demonstrated to have limited efficacy. The present study examined the combined inhibition of MET and SRC kinase activity in colon cancer cells. Furthermore, the role of the HGF/MET pathway in ligand-dependent and -independent activation was demonstrated. The single inhibition of MET by knockdown small interfering RNA or inhibitor indicated a limited anti-viability effects without inhibiting the basal phosphorylation levels of SRC, protein kinase B (AKT) or extracellular signal-regulated kinase (ERK)...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#5
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807057/inhibitory-effects-of-hnf4%C3%AE-on-migration-maltransformation-of-hepatic-progenitors-hnf4%C3%AE-overexpressing-hepatic-progenitors-for-liver-repopulation
#6
Ping Wang, Min Cong, Tianhui Liu, Hufeng Xu, Lin Wang, Guangyong Sun, Aiting Yang, Dong Zhang, Jian Huang, Yameng Sun, Wenshan Zhao, Hong Ma, Jidong Jia, Hong You
BACKGROUND: Although they are expandable in vitro, hepatic progenitors are immature cells and share many immunomarkers with hepatocellular carcinoma, raising potential concerns regarding maltransformation after transplantation. This study investigated the effects of hepatic nuclear factor (HNF) 4α on the proliferation, migration, and maltransformation of hepatic progenitors and determined the feasibility of using these manipulated cells for transplantation. METHODS: The effects of HNF4α on rat hepatic progenitors (i...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28805978/obeticholic-acid-a-selective-farnesoid-x-receptor-agonist-regulates-bile-acid-homeostasis-in-sandwich-cultured-human-hepatocytes
#7
Yuanyuan Zhang, Jonathan P Jackson, Robert L St Claire, Kimberly Freeman, Kenneth R Brouwer, Jeffrey E Edwards
Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28802864/%C3%AE-3-adrenergic-receptor-regulates-hepatic-apolipoprotein-a-i-gene-expression
#8
Xiaojing Cao, Yanfang Li
BACKGROUND: β3-adrenergic receptor (β3-AR) was shown to upregulate hepatic apolipoprotein A-I (apoA-I) expression and reverse atherosclerotic plaques in vivo experiments. However, the effect of β3-AR on apoA-I expression in vitro is unknown. The specific mechanism underlying β3-AR prevention of atherosclerosis is unclear. OBJECTIVE: The present study was designed to investigate the molecular mechanism of β3-AR-mediated regulation of hepatic apoA-I gene expression...
July 27, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28790147/hepatocyte-specific-deletion-of-egfr-in-mice-reduces-hepatic-abcg2-transport-activity-measured-with-11-c-erlotinib-and-positron-emission-tomography
#9
Alexander Traxl, Karin Komposch, Elisabeth Glitzner, Thomas Wanek, Severin Mairinger, Oliver Langer, Maria Sibilia
The epidermal growth factor receptor (EGFR) regulates cellular expression levels of breast cancer resistance protein (humans: ABCG2, rodents: Abcg2) via its downstream signaling pathways. Drugs that inhibit EGFR signaling (e.g. tyrosine kinase inhibitors, antibodies) may lead to ABCG2-mediated drug-drug interactions (DDIs) by changing disposition of concomitantly administered ABCG2 substrate drugs. In this study we used positron emission tomography (PET)/magnetic resonance (MR) imaging to compare disposition of the model Abcg2 substrate [(11)C]erlotinib in a mouse model of hepatocyte-specific deletion of EGFR (EGFR(Δhep) mice, n = 5) with EGFR(fl/fl) control mice (n = 6), which have normal EGFR expression levels in all tissues...
August 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28783177/autophagy-dependent-generation-of-axin2-cancer-stem-like-cells-promotes-hepatocarcinogenesis-in-liver-cirrhosis
#10
J Li, S B Hu, L Y Wang, X Zhang, X Zhou, B Yang, J H Li, J Xiong, N Liu, Y Li, Y Z Wu, Q C Zheng
Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28780159/pyridine-pyrimidine-amides-that-prevent-hgf-induced-epithelial-scattering-by-two-distinct-mechanisms
#11
Adam Siddiqui-Jain, Jacob P Hoj, J Blade Hargiss, Taylor H Hoj, Carter J Payne, Collin A Ritchie, Steven R Herron, Colette Quinn, Jeffrey T Schuler, Marc D H Hansen
Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in individual cells detaching and assuming a migratory and invasive phenotype. Epithelial scattering recapitulates cancer progression and studies have implicated HGF signaling as a driver of cancer metastasis. Inhibitors of HGF signaling have been proposed to act as anti-cancer agents. We previously screened a small molecule library for compounds that block HGF-induced epithelial scattering. Most hits identified in this screen exhibit anti-mitotic properties...
July 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28766361/annals-express-diagnostic-specificity-and-sensitivity-of-pivkaii-gp3-cstb-scca1-and-hgf-for-diagnosis-of-hepatocellular-carcinoma-in-patients-with-alcoholic-liver-cirrhosis
#12
Adriana Unic, Lovorka Derek, Marko Duvnjak, Leonardo Patrlj, Mislav Rakic, Milan Kujundzic, Vesna Renjic, Nikola Stokovic, Petra Dinjar, Anita Jukic, Ivica Grgurevic
INTRODUCTION: Despite of some new treatment possibilities the improvement in survival rate for hepatocellular carcinoma (HCC) patients is still poor due to late diagnosis. The aim of this study was to investigate diagnostic sensitivity and specificity of Protein induced by vitamin K absence or antagonist-II (PIVKAII), Glypican-3 (GP3), Cystatin B (CSTB), Squamous cell carcinoma antigen 1 (SCCA1) and Hepatocyte growth factor (HGF) as potential tumour markers for HCC in patients with alcoholic liver cirrhosis (ALC) using imaging techniques (MSCT and MRI) as reference standards...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28765687/can-a-fibrotic-liver-afford-epithelial-mesenchymal-transition
#13
EDITORIAL
Stefan Munker, Yong-Le Wu, Hui-Guo Ding, Roman Liebe, Hong-Lei Weng
The question whether epithelial-mesenchymal transition (EMT) occurs during liver fibrogenesis is a controversial issue. In vitro studies confirm that hepatocytes or cholangiocytes undergo EMT upon transforming growth factor β (TGF-β) stimulation, whereas in vivo experiments based on genetic fate mapping of specific cell populations suggest that EMT does not occur in fibrotic animal models. In this review we present current data supporting or opposing EMT in chronic liver disease and discuss conditions for the occurrence of EMT in patients...
July 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28763748/the-therapeutic-effects-of-yongdamsagan-tang-on-autoimmune-hepatitis-models
#14
Jiyoung Park, Hayeon Kim, In-Seung Lee, Kang-Hoon Kim, Yumi Kim, Yun-Cheol Na, Jang-Hoon Lee, Hyeung-Jin Jang
Autoimmune hepatitis (AIH) is an immunity disorder that is the result of antibodies in the liver tissue of the patient that are attacked by activated immune cells due to an unknown cause. In this study, we aimed to investigate the anti-inflammatory effect of Yongdamsagan-tang (YST) extracts and confirm effects on autoimmune hepatitis models as the therapeutic agent using the YST extracted by various solvents. YST, a mixture of 11 herbal extracts, is known in traditional Korean medicine as a widely used treatment for inflammatory diseases...
July 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28759733/protective-effect-of-rimonabant-a-canabinoid-receptor-1-antagonist-on-nonalcoholic-fatty-liver-disease-in-a-rat-model-by-modulating-the-hepatic-expression-of-activin-a-and-follistatin
#15
Noha Ibrahim Hussien, Hanan I El-Kerdasy, Mohamed El-Tantawy Ibrahim
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality with no proven effective therapy yet. Endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. The present study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced by choline deficient (CD) diet in rats, as well as to detect whether it can modulate the hepatic expression of activin A and follistatin or not...
July 31, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28758209/distinct-projection-targets-define-subpopulations-of-mouse-brainstem-vagal-neurons-that-express-the-autism-associated-met-receptor-tyrosine-kinase
#16
Anna Kamitakahara, Hsiao-Huei Wu, Pat Levitt
Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell-type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET-expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract...
July 31, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28757162/an-in%C3%A2-vitro-human-liver-model-by-ipsc-derived-parenchymal-and-non-parenchymal-cells
#17
Yuta Koui, Taketomo Kido, Toshimasa Ito, Hiroki Oyama, Shin-Wei Chen, Yuki Katou, Katsuhiko Shirahige, Atsushi Miyajima
During liver development, hepatoblasts and liver non-parenchymal cells (NPCs) such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) constitute the liver bud where they proliferate and differentiate. Accordingly, we reasoned that liver NPCs would support the maturation of hepatocytes derived from human induced pluripotent stem cells (hiPSCs), which usually exhibit limited functions. We found that the transforming growth factor β and Rho signaling pathways, respectively, regulated the proliferation and maturation of LSEC and HSC progenitors isolated from mouse fetal livers...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28752455/protocol-for-directed-differentiation-of-human-induced-pluripotent-stem-cells-ipscs-to-a-hepatic-lineage
#18
Joseph E Kaserman, Andrew A Wilson
Directed differentiation is a powerful cell culture technique where developmental pathways are applied to a pluripotent progenitor in order to generate specific terminally differentiated cell populations. Here, we describe a serum-free protocol using growth factors in defined concentrations to derive iPSC-hepatic cells starting from both feeder and feeder-free conditions. The generated iPSC-hepatic cells are developmentally similar to fetal stage hepatocytes, and when generated from patients with genetic mutations such as alpha-1 antitrypsin deficiency recapitulate pathologic changes associated with clinical disease, such as protein misfolding, intracellular retention of misfolded proteins, and elevated levels of ER stress...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28751869/alterations-of-growth-factors-in-autism-and-attention-deficit-hyperactivity-disorder
#19
Alma Y Galvez-Contreras, Tania Campos-Ordonez, Rocio E Gonzalez-Castaneda, Oscar Gonzalez-Perez
Growth factors (GFs) are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF), glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28751311/identification-of-a-novel-population-of-highly-cytotoxic-c-met-expressing-cd8-t-lymphocytes
#20
Mahdia Benkhoucha, Nicolas Molnarfi, Gürkan Kaya, Elodie Belnoue, Kristbjörg Bjarnadóttir, Pierre-Yves Dietrich, Paul R Walker, Denis Martinvalet, Madiha Derouazi, Patrice H Lalive
CD8(+) cytotoxic T lymphocytes (CTLs) are critical mediators of anti-tumor immunity, and controlling the mechanisms that govern CTL functions could be crucial for enhancing patient outcome. Previously, we reported that hepatocyte growth factor (HGF) limits effective murine CTL responses via antigen-presenting cells. Here, we show that a fraction of murine effector CTLs expresses the HGF receptor c-Met (c-Met(+) CTLs). Phenotypic and functional analysis of c-Met(+) CTLs reveals that they display enhanced cytolytic capacities compared to their c-Met(-) CTL counterparts...
July 27, 2017: EMBO Reports
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