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TGF beta in liver fibrosis

Piero Pingitore, Paola Dongiovanni, Benedetta Maria Motta, Marica Meroni, Saverio Massimo Lepore, Rosellina Margherita Mancina, Serena Pelusi, Cristina Russo, Andrea Caddeo, Giorgio Rossi, Tiziana Montalcini, Arturo Pujia, Olov Wiklund, Luca Valenti, Stefano Romeo
Liver fibrosis is a pathological scarring response to chronic hepatocellular injury and hepatic stellate cells (HSCs) are key players in this process. PNPLA3 I148M is a common variant robustly associated with liver fibrosis but the mechanisms underlying this association are unknown.We aimed to examine a) the effect of fibrogenic and proliferative stimuli on PNPLA3 levels in HSCs and b) the role of wild type and mutant PNPLA3 overexpression on markers of HSC activation and fibrosis.Here we show that PNPLA3 is upregulated by the fibrogenic cytokine transforming growth factor-beta (TGF-β), but not by platelet-derived growth factor (PDGF), and is involved in the TGF-β-induced reduction in lipid droplets in primary human HSCs...
October 13, 2016: Human Molecular Genetics
Yuan-Yuan Zhan, Jin-Hui Wang, Xing Tian, Shi-Xiu Feng, Lin Xue, Li-Ping Tian
ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao, was also known as watermelon belongs to family Cucurbitaceae, variously used as healthy food and in the treatment of liver and lungs problems. Currently, Citrullus lanatus has become a major economic crop of medicinal and edible effects with regional characteristics. AIM: This study was designed to evaluate the hepatoprotective and antioxidant activity of the seed melon (Citrullus lanatus ssp...
October 4, 2016: Journal of Ethnopharmacology
Cui Yang, Si-Dao Zheng, Hong-Jin Wu, Shao-Jun Chen
OBJECTIVE: MicroRNAs (miRNAs or miRs) play critical roles in the fibrotic process in different organs. We summarized the latest research progress on the roles and mechanisms of miRNAs in the regulation of the molecular signaling pathways involved in fibrosis. DATA SOURCES: Papers published in English from January 2010 to August 2015 were selected from the PubMed and Web of Science databases using the search terms "microRNA", "miR", "transforming growth factor β", "tgf β", "mitogen-activated protein kinase", "mapk", "integrin", "p38", "c-Jun NH2-terminal kinase", "jnk", "extracellular signal-regulated kinase", "erk", and "fibrosis"...
2016: Chinese Medical Journal
Nagla A El-Sherbeeny, Manar A Nader, Ghalia M Attia, Hayam Ateyya
Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates...
September 16, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Ganping Bai, Guohe Yan, Guojian Wang, Ping Wan, Ronghua Zhang
Hepatic fibrosis (HF), a wound-healing response to a variety of chronic stimuli, is characterized by the excessive synthesis of extracellular matrix (ECM) proteins by hepatic stellate cells (HSC) and eventually the development of hepatic cirrhosis. Turtle shell pill (TSP) is a common traditional Chinese medicine used for preventing and treating HF and early hepatic cirrhosis, but its side-effects and the shortage of ingredients limit its clinical application. In addition, its mechanism of action is not clear...
September 9, 2016: Oncology Reports
Sung-Bae Lee, Hyeong-Geug Kim, Hyo-Seon Kim, Jin-Seok Lee, Hwi-Jin Im, Won-Yong Kim, Chang-Gue Son
Amomum xanthioides has been traditionally used to treat diverse digestive system disorders in the Asian countries. We investigated antihepatofibrotic effects of ethyl acetate fraction of Amomum xanthioides (EFAX). Liver fibrosis is induced by dimethylnitrosamine (DMN) injection (intraperitoneally, 10 mg/kg of DMN for 4 weeks to Sprague-Dawley rats). EFAX (25 or 50 mg/kg), silymarin (50 mg/kg), or distilled water was orally administered every day. The DMN injection drastically altered body and organ mass, serum biochemistry, and platelet count, while EFAX treatment significantly attenuated this alteration...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Na Fu, Xuemin Niu, Yang Wang, Huijuan Du, Baoyu Wang, Jinghua Du, Ya Li, Rongqi Wang, Yuguo Zhang, Suxian Zhao, Dianxing Sun, Liang Qiao, Yuemin Nan
Long non-coding RNA (LncRNA)-activated by transforming growth factor-beta (LncRNA-ATB) is a key regulator of transforming growth factor-beta (TGF-β) signaling pathway, and is positively correlated with the development of liver cirrhosis and vascular invasion of hepatocellular carcinoma (HCC). However, the role of LncRNA-ATB in hepatitis C virus (HCV)-related liver fibrosis remains largely unknown. In the present study, we confirmed a high expression level of LncRNA-ATB in the liver tissues and plasma samples of patients with HCV-related hepatic fibrosis, and the plasma level of LncRNA-ATB was significantly correlated with liver fibrosis stages...
August 2016: Discovery Medicine
Mohamed G Elsakkar, Maha M Eissa, Wafaa A Hewedy, Rasha M Nassra, Soha F Elatrebi
AIMS: This study explores the potential antifibrotic effect of sodium valproate (SV), an inhibitor of class I histone deacetylase (HDAC) enzymes, and/or praziquantel (PZQ) on Schistosoma mansoni (S. mansoni)-induced liver fibrosis in mice. MAIN METHODS: Male Swiss albino mice were divided into nine groups: group I- normal control (NC); group II- uninfected gum mucilage (GM) treated; group III- uninfected PZQ- treated; group IV- uninfected SV-treated; group V- control S...
October 1, 2016: Life Sciences
Zhiqiang Zheng, Richard W Gelling
Advanced liver disease (ALD) is often characterized with overt malnutrition and liver fibrosis. In this study, a dietary supplement (DS) was first developed, including branch chain amino acids, fat soluble vitamins, zinc, medium chain triglycerides, soy lecithin, L-carnitine, and n-3 polyunsaturated fatty acids. Benefits of DS were then tested using an ALD rat model treated with carbon tetrachloride (CCl4) for 6, 8, and 10 weeks, respectively. Our study showed that CCl4-induced drop of serum albumin and ratio of branch chain to aromatic amino acids were significantly prevented at all three time points...
July 29, 2016: Journal of Dietary Supplements
Silke Leiting, Sebastian Seidl, Adoracion Martinez-Palacian, Lars Muhl, Sandip M Kanse
Deletion of the Habp2 gene encoding Factor VII-activating protease (FSAP) increases liver fibrosis in mice. A single nucleotide polymorphism (G534E) in HABP2 leads to lower enzymatic activity and is associated with enhanced liver fibrosis in humans. Liver fibrosis is associated with a decrease in FSAP expression but, to date, nothing is known about how this might be regulated. Primary mouse hepatocytes or the hepatocyte cell line, AML12, were treated with different factors, and expression of FSAP was determined...
September 30, 2016: Journal of Biological Chemistry
Ying-Hua He, Zeng Li, Ming-Ming Ni, Xing-Yan Zhang, Ming-Fang Li, Xiao-Ming Meng, Cheng Huang, Jun Li
Liver fibrosis is a worldwide problem with a significant morbidity and mortality. Cryptolepis sanguinolenta (family Periplocaceae) is widely used in West African countries for the treatment of malaria, as well as for some other diseases. However, the role of C. sanguinolenta in hepatic fibrosis is still unknown. It has been reported that Methyl-CpG binding protein 2 (MeCP2) had a high expression in liver fibrosis and played a central role in its pathobiology. Interestingly, we found that a cryptolepine derivative (HZ-6h) could inhibit liver fibrosis by reducing MeCP2 expression, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) in protein levels in vitro...
September 2016: Canadian Journal of Physiology and Pharmacology
Memy H Hassan, Mohamed M Ghobara
This study was aimed at investigating the antifibrotic effect of meloxicam in CCl4-induced liver fibrosis and elucidating its underlying mechanism. Forty male rats were equally randomized for 8-week treatment with corn oil (negative control), CCl4 (to induce liver fibrosis), and/or meloxicam. Meloxicam effectively ameliorated the CCl4-induced alterations in liver histology, liver weight to body weight ratio, liver functions, and serum markers for liver fibrosis (hyaluronic acid, laminin, and PCIII). Meloxicam significantly abrogated CCl4-induced elevation of messenger RNA (mRNA) expressions for collagen I and alpha smooth muscle actin (α-SMA) and hepatic contents of hydroxyproline, transforming growth factor beta (TGF-β), and tissue inhibitor of matrix metalloproteases (TIMP-1)...
September 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Aya Mohammed, Ekram N Abd Al Haleem, Wesam M El-Bakly, Ebtehal El-Demerdash
Several chronic liver diseases can lead to the occurrence of hepatic fibrosis through the accumulation of iron, which causes induction of oxidative stress and consequently activation of fibrogenesis. The present study was designed to investigate the potential antifibrotic and anti-oxidant effects of deferoxamine (DFO), a well-known iron chelator in an experimental rat model of liver injury using carbon tetrachloride (CCl4 ). First, the potential effective dose of DFO was screened against CCl4 -induced acute hepatotoxicity...
August 2016: Clinical and Experimental Pharmacology & Physiology
Vu Thi Thu, Hyoung Kyu Kim, Le Thanh Long, To Thanh Thuy, Nguyen Quang Huy, Soon Ha Kim, Nari Kim, Kyung Soo Ko, Byoung Doo Rhee, Jin Han
Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models...
May 2016: Korean Journal of Physiology & Pharmacology
Jingjing Jiao, Kohtaro Ooka, Holger Fey, Maria Isabel Fiel, Adeeb H Rahmman, Kensuke Kojima, Yujin Hoshida, Xintong Chen, Tatiana de Paula, Diana Vetter, David Sastre, Ka Hin Lee, Youngmin A Lee, Meena Bansal, Scott L Friedman, Miriam Merad, Costica Aloman
BACKGROUND & AIMS: Interleukin-15 (IL-15) and its high affinity receptor interleukin-15 receptor alpha (IL-15Rα) are widely expressed in immune cells and hepatic resident cells. IL-15 signaling has important functions in homeostasis of natural killer (NK), natural killer T (NKT) and cytotoxic T (CD8(+) T) cells, and in liver regeneration. We hypothesized that IL-15 has a protective role in liver fibrosis progression by maintaining NK cell homeostasis. METHODS: Fibrosis was induced using two mechanistically distinct models...
August 2016: Journal of Hepatology
Suzy Fayez Ewida, Asmaa Gaber Abdou, Amal Abd El-Rasol Elhosary, Shaimaa Abd El-Ghane Metawe
It is still a matter of debate as to whether in vitro mesenchymal stem cell (MSC)-derived hepatocytes may efficiently repopulate a host liver to provide adequate functional substitution. The aim of this study is to assess the efficacy and consistency of in vitro hepatic differentiation from Wharton jelly-derived MSCs, and to validate their therapeutic potential in experimentally induced liver fibrosis compared with nondifferentiated MSCs. Forty adult male albino rats were divided into 4 main groups: (I) normal control group; (II) carbon tetrachloride (CCl4)-treated group (injected CCl4 solution twice a week for 8 wk); (III) MSC-treated group (a single intravenous dose of MSCs from human umbilical cord at the fourth week of induction of fibrosis); and (IV) hepatocyte-like stem cells (HLCs)-treated group (a single intravenous dose of MSCs after in vitro conversion to hepatocyte at the fourth week of induction of fibrosis)...
May 5, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Y Qin, Q Wang, Y Zhong, F Zhao, F Wu, Y Wang, T Ma, C Liu, H Bian, Z Li
Proteins N-glycosylation is significantly increased in the activated human hepatic stellate cells (HSCs) stimulated by transforming growth factor-β1 (TGF-β1) compared to the quiescent HSCs according to our previous study. However, little is known about the alteration of N-glycoprotein profiles in the activated HSCs. Profiles of N-glycopeptides / N-glycoproteins / N-glycosites in LX-2 cells, with and without activation by TGF-β1, were identified and compared using hydrazide chemistry enrichment coupled with liquid chromatography - mass spectrometry analysis...
2016: Cellular and Molecular Biology
Norihisa Nishimura, Mitsuteru Kitade, Ryuichi Noguchi, Tadashi Namisaki, Kei Moriya, Kosuke Takeda, Yasushi Okura, Yosuke Aihara, Akitoshi Douhara, Hideto Kawaratani, Kiyoshi Asada, Hitoshi Yoshiji
BACKGROUND: It is widely understood that insulin resistance (IR) critically correlates with the development of liver fibrosis in several types of chronic liver injuries. Several experiments have proved that anti-IR treatment can alleviate liver fibrosis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules, improving IR. The aim of this study was to elucidate the effect of an SGLT2 inhibitor on the development of liver fibrosis using obese diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and their littermate nondiabetic Long-Evans Tokushima Otsuka (LETO) rats...
March 29, 2016: Journal of Gastroenterology
Chan Zhou, Samuel R York, Jennifer Y Chen, Joshua V Pondick, Daniel L Motola, Raymond T Chung, Alan C Mullen
BACKGROUND: Hepatic fibrosis is the underlying cause of cirrhosis and liver failure in nearly every form of chronic liver disease, and hepatic stellate cells (HSCs) are the primary cell type responsible for fibrosis. Long noncoding RNAs (lncRNAs) are increasingly recognized as regulators of development and disease; however, little is known about their expression in human HSCs and their function in hepatic fibrosis. METHODS: We performed RNA sequencing and ab initio assembly of RNA transcripts to define the lncRNAs expressed in human HSC myofibroblasts...
2016: Genome Medicine
Jingjing Li, Kan Chen, Sainan Li, Jiao Feng, Tong Liu, Fan Wang, Rong Zhang, Shizan Xu, Yuqing Zhou, Shunfeng Zhou, Yujing Xia, Jie Lu, Yingqun Zhou, Chuanyong Guo
Liver fibrosis is a dynamic reversible pathological process in the development of chronic liver disease to cirrhosis. However, the current treatments are not administered for a long term due to their various side effects. Autophagy is initiated to decompose damaged or excess organelles, which had been found to alter the progression of liver fibrosis. In this article, we hypothesized that fucoidan from Fucus vesiculosus may attenuate liver fibrosis in mice by inhibition of the extracellular matrix and autophagy in carbon tetrachloride- and bile duct ligation-induced animal models of liver fibrosis...
2016: Drug Design, Development and Therapy
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