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TGF beta in liver fibrosis

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https://www.readbyqxmd.com/read/29406047/iron-enhances-hepatic-fibrogenesis-and-activates-transforming-growth-factor-%C3%AE-signaling-in-murine-hepatic-stellate-cells
#1
Kosha J Mehta, Jason D Coombes, Marco Briones-Orta, Paul P Manka, Roger Williams, Vinood B Patel, Wing-Kin Syn
BACKGROUND: Although excess iron induces oxidative stress in the liver, it is unclear whether it directly activates the hepatic stellate cells (HSC). MATERIALS AND METHODS: We evaluated the effects of excess iron on fibrogenesis and transforming growth factor beta (TGF-β) signaling in murine HSC. Cells were treated with holotransferrin (0.005-5g/L) for 24 hours, with or without the iron chelator deferoxamine (10µM). Gene expressions (α-SMA, Col1-α1, Serpine-1, TGF-β, Hif1-α, Tfrc and Slc40a1) were analyzed by quantitative real time-polymerase chain reaction, whereas TfR1, ferroportin, ferritin, vimentin, collagen, TGF-β RII and phospho-Smad2 proteins were evaluated by immunofluorescence, Western blot and enzyme-linked immunosorbent assay...
February 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29402841/the-role-of-signal-transducer-and-activator-of-transcription-5-and-transforming-growth-factor-beta-1-in-hepatic-fibrosis-induced-by-chronic-hepatitis-c-virus-infection-in-egyptian-patients
#2
Mona A Abu El Makarem, Ghada M El-Sagheer, Moustafa A Abu El-Ella
<br>To investigate the possible role of STAT5 in the pathogenesis of liver fibrosis in Egyptian patients with chronic hepatitis C (CHC) virus infection and its relation to hepatic stellate cells (HSCs). <br> Materials (Subjects) and Methods<br>Sixty-five patients (46/19 male/ female ratio) were divided into 4 groups based on the severity of fibrosis as detected by fibroscan, (15 F1, 21 F2, 13 F3, and 16 F4). Twenty, age- and gender-matched, healthy persons volunteered as a control. The serum levels of STAT5, TGF-β1, α-SMA, fasting blood sugar (FBS), fasting insulin and homeostasis model assessments of insulin resistance (HOMA-IR) were determined and compared for all groups...
January 31, 2018: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
https://www.readbyqxmd.com/read/29331278/impact-of-treatment-with-a-protein-tyrosine-kinase-inhibitor-genistein-on-acute-and-chronic-experimental-schistosoma-mansoni-infection
#3
Maysa Mohamed Kamel Sobhy, Soheir Sayed Mahmoud, Shaimaa Helmy El-Sayed, Enas Mohamed Ali Rizk, Amira Raafat, Mohamed Sherif Ismail Negm
Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease...
January 10, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29250925/cucurbitacin-b-attenuates-ccl4-induced-hepatic-fibrosis-in-mice-through-inhibition-of-stat-3
#4
Alaliaa M Sallam, Ahmed Esmat, Ashraf B Abdel-Naim
Liver fibrosis is a major health concern worldwide. Inhibitors of Signal Transducer and Activator of Transcription 3 (STAT3) have been reported to attenuate experimental liver fibrosis. Therefore, the aim of current study was to investigate the potential ameliorative effect of cucurbitacin-B (Cucu-B) against CCl4 -induced liver fibrosis in mice. Treatment with Cucu-B (5 mg/kg) preserved hepatocellular membrane integrity and amended the metabolic function as indicated by preventing the rise of serum liver function markers...
December 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29232404/antioxidant-antiapoptotic-and-amino-acid-balance-regulating-activities-of-1-7-dihydroxy-3-4-8-trimethoxyxanthone-against-dimethylnitrosamine-induced-liver-fibrosis
#5
Xi-Yuan Zheng, Xin Zhao, Ying-Fan Yang, Han-Jie Jiang, Wan Li, Yi Sun, Xiao-Ping Pu
Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injury which could be caused by viral, autoimmune, drugs, and so on. Unfortunately, there was no effective therapy available for liver fibrosis in clinic. In this study, we identified the anti-fibrotic effects of 1,7-dihydroxy-3,4,8-trimethoxyxanthone (ZYC-1) on the dimethylnitrosamine (DMN)-induced rat model. ZYC-1 was isolated from Swertia punicea Hemsl and was administrated to DMN-induced rat model. ZYC decreased the hyaluronic acid (HA), type IV collagen (CIV) and hydroxyproline (Hyp) levels and inhibited the expression of α smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-1β)...
2017: PloS One
https://www.readbyqxmd.com/read/29155473/relationship-between-hepatic-progenitor-cells-and-stellate-cells-in-chronic-hepatitis-c-genotype-4
#6
Thanaa El Sayed Ahmed Helal, Nermine Ahmed Ehsan, Nehal Ahmed Radwan, Eman Abdelsameea
Hepatitis C virus (HCV) infection represents a major health problem in many areas of the world, especially Egypt. Hepatic progenitor cells (HPCs) and hepatic stellate cells (HSCs) have been implicated in fibrosis progression in chronic HCV. The aim of this study was to investigate the role of HPCs and HSCs in chronic HCV infection and the relationship between both cell types. This retrospective study was conducted on 100 chronic HCV patients. Immunohistochemistry was performed on liver tissue sections for cytokeratin 19 (progenitor cell markers), smooth muscle actin (stellate cell markers), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta (TGF-ß)...
November 20, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/29152065/kahweol-decreases-hepatic-fibrosis-by-inhibiting-the-expression-of-connective-tissue-growth-factor-via-the-transforming-growth-factor-beta-signaling-pathway
#7
Hye-Young Seo, Yun-A Jung, So-Hee Lee, Jae Seok Hwang, Keun-Gyu Park, Mi-Kyung Kim, Byoung Kuk Jang
Kahweol is a diterpene molecule found in Coffea Arabica beans. Previous studies have shown that coffee reduces liver fibrosis, but it is not clear which component of coffee has the protective effect. In this study, we examined whether kahweol has a protective effect on hepatic fibrosis in vivo and in vitro. Kahweol decreased hepatic fibrosis by inhibiting connective tissue growth factor (CTGF) expression in thioacetamide (TAA)-treated mice. The expression of phospho-Smad3, signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal protein kinase (JNK) increased in the livers of TAA-treated mice and decreased in the kahweol-treated group...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150921/tgf-%C3%AE-and-hepatocellular-carcinoma-when-a-friend-becomes-an-enemy
#8
Marco Arrese, Daniel Cabrera, Alejandra Hernandez, Luis Astete, Lisbell Estrada, Claudio Cabello-Verrugio
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide accounting for more than 700 thousand deaths per year. Most of the HCC develops in a cirrhotic liver, a microenvironment where fibrotic tissue replaces parenchymal cells. Thus, there is a close connection between fibrosis and HCC development. Understanding the cellular and molecular mechanisms involved in this process is a crucial step to advance in novel therapeutic or pharmacological strategies to prevent or improve the course of this malignancy...
November 16, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28965860/hepatic-stellate-cell-targeted-imatinib-nanomedicine-versus-conventional-imatinib-a-novel-strategy-with-potent-efficacy-in-experimental-liver-fibrosis
#9
Nesrine S El-Mezayen, Wessam F El-Hadidy, Wessam M El-Refaie, Th I Shalaby, Mahmoud M Khattab, Aiman S El-Khatib
Liver fibrosis is a global health problem without approved treatment. Imatinib inhibits two key profibrotic pathways; platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) and thus can be used to treat liver fibrosis. However, conventional imatinib therapy is hampered by low concentration at target tissue and increased toxicity to other tissues especially heart, lung and liver. Since hepatic stellate cells (HSCs) are the main contributors to liver fibrosis pathogenesis and sole hepatic vitamin A (VA) storage cells, they can be actively targeted by coupling liposomes to VA...
September 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28918914/analysis-of-genomes-and-transcriptomes-of-hepatocellular-carcinomas-identifies-mutations-and-gene-expression-changes-in-the-transforming-growth-factor-%C3%AE-pathway
#10
Jian Chen, Sobia Zaidi, Shuyun Rao, Jiun-Sheng Chen, Liem Phan, Patrizia Farci, Xiaoping Su, Kirti Shetty, Jon White, Fausto Zamboni, Xifeng Wu, Asif Rashid, Nagarajan Pattabiraman, Raja Mazumder, Anelia Horvath, Ray-Chang Wu, Shulin Li, Cuiying Xiao, Chu-Xia Deng, David A Wheeler, Bibhuti Mishra, Rehan Akbani, Lopa Mishra
BACKGROUND & AIMS: Development of hepatocellular carcinoma (HCC) is associated with alterations in the transforming growth factor-beta (TGF-β) signaling pathway, which regulates liver inflammation and can have tumor suppressor or promoter activities. Little is known about the roles of specific members of this pathway at specific of HCC development. We took an integrated approach to identify and validate the effects of changes in this pathway in HCC and identify therapeutic targets. METHODS: We performed transcriptome analyses for a total of 488 HCCs that include data from The Cancer Genome Atlas...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28789951/hepatoprotective-activities-of-rosmarinic-acid-against-extrahepatic-cholestasis-in-rats
#11
Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Su-Lan Liao, Su-Tze Chou, Ching-Ping Yang, Chun-Jung Chen
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3...
August 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28659031/gypenosides-ameliorate-carbon-tetrachloride-induced-liver-fibrosis-by-inhibiting-the-differentiation-of-hepatic-progenitor-cells-into-myofibroblasts
#12
Jiamei Chen, Xuewei Li, Yonghong Hu, Wei Liu, Qun Zhou, Hua Zhang, Yongping Mu, Ping Liu
Gypenosides (GPs), the predominant components of Gynostemma pentaphyllum, exert antifibrotic effects; however, the mechanisms underlying their ability to ameliorate liver fibrosis are unclear. Liver fibrosis was induced in C57BL/6 mice via subcutaneous injection of 10% carbon tetrachloride (CCl[Formula: see text] three times a week for two weeks. Then, CCl4 was administered in conjunction with intragastric GPs for another three weeks. For in vitro analyses, WB-F344, hepatatic progenitor cells (HPCs) were treated with transforming growth factor beta 1 (TGF-[Formula: see text]1) with or without GPs for 48[Formula: see text]h...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28642549/focal-adhesion-kinase-regulates-hepatic-stellate-cell-activation-and-liver-fibrosis
#13
Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638086/wnt2b-attenuates-hscs-activation-and-liver-fibrosis-through-negative-regulating-tlr4-signaling
#14
Yi Yuan, Qiuju Han, Siyu Li, Zhigang Tian, Jian Zhang
The Wingless-type MMTV integration site family member 2b (Wnt2b) has been found to be a principal mediator of liver development and regeneration. However, the significance of Wnt2b in the pathogenesis of fibrosis-related liver diseases remains undefined. Here, we report that Wnt2b was highly expressed in the fibrotic liver tissues, exhibiting protective effects against activation of hepatic stellate cells (HSCs) and fibrosis progression. We identified a negative regulation of Wnt2b on the toll-like receptor 4 (TLR4) activation-mediated pro-fibrogenic effects...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28561587/protective-effects-of-functional-chicken-liver-hydrolysates-against-liver-fibrogenesis-antioxidation-anti-inflammation-and-antifibrosis
#15
Po-Ju Chen, Jung-Kai Tseng, Yi-Ling Lin, Yi-Hsieng Samuel Wu, Yi-Tse Hsiao, Jr-Wei Chen, Yi-Chen Chen
Via an assay using an Amino Acid Analyzer, pepsin-digested chicken liver hydrolysates (CLHs) contain taurine (365.57 ± 39.04 mg/100 g), carnosine (14.03 ± 1.98 mg/100 g), and anserine (151.58 ± 27.82 mg/100 g). This study aimed to evaluate whether CLHs could alleviate thioacetamide (TAA)-induced fibrosis. A dose of 100 mg TAA/kg BW significantly increased serum liver damage indices and liver cytokine contents. Cell infiltration and monocytes/macrophages in livers of TAA-treated rats were illustrated by the H&E staining and immunohistochemical analysis of cluster of differentiation 68 (CD68, ED1), respectively...
June 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28538192/hepatic-anti-inflammatory-effect-of-hexane-extracts-of-dioscorea-batatas-decne-possible-suppression-of-toll-like-receptor-4-mediated-signaling
#16
Hyun Jung Koo, SungRyul Lee, Kwang Jin Chang, Eunsoo Sohn, Eun-Hwa Sohn, Se Chan Kang, Suhkneung Pyo
The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-β1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28518142/mir-130a-3p-attenuates-activation-and-induces-apoptosis-of-hepatic-stellate-cells-in-nonalcoholic-fibrosing-steatohepatitis-by-directly-targeting-tgfbr1-and-tgfbr2
#17
Yang Wang, Jinghua Du, Xuemin Niu, Na Fu, Rongqi Wang, Yuguo Zhang, Suxian Zhao, Dianxing Sun, Yuemin Nan
Nonalcoholic fibrosing steatohepatitis is a uniform process that occurs throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been shown to be involved in the biological processes, but the role and molecular mechanism of miRNAs in NAFLD are not entirely clear. In this study, we observed a significant reduction in the expression of miR-130a-3p in livers of a mouse model with fibrosis induced by a methionine-choline-deficient diet, of NAFLD patients, and in activated hepatic stellate cells (HSCs)...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28467108/gremlin1-accelerates-hepatic-stellate-cell-activation-through-upregulation-of-tgf-beta-expression
#18
Yan-Qiong Zhang, Lin-Yan Wan, Xiao-Min He, Yi-Ran Ni, Chang Wang, Chang-Bai Liu, Jiang-Feng Wu
Gremlin1, the antagonist of bone morphogenetic protein-7 and one of the target genes of transforming growth factor (TGF)-β signal pathway, plays an important role in embryonic development and its expression decreases along with aging. To explore the expression of gremlin1 in liver fibrosis and the causal link between gremlin1 and hepatic stellate cell (HSC) activation, we detected the expression of gremlin1 in mice with hepatic fibrosis induced by porcine serum using real time quantitative PCR (RT-qPCR) and immunohistochemical staining...
July 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28424263/the-kielin-chordin-like-protein-kcp-attenuates-high-fat-diet-induced-obesity-and-metabolic-syndrome-in-mice
#19
Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications such as insulin resistance and non-alcoholic fatty liver disease are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The kielin/chordin-like protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28416441/glechoma-hederacea-extracts-attenuate-cholestatic-liver-injury-in-a-bile-duct-ligated-rat-model
#20
Ya-Yu Wang, Shih-Yi Lin, Wen-Ying Chen, Su-Lan Liao, Chih-Cheng Wu, Pin-Ho Pan, Su-Tze Chou, Chun-Jung Chen
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea. AIM OF THE STUDY: This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats. MATERIALS AND METHODS: Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats...
April 14, 2017: Journal of Ethnopharmacology
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