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Smad AND Hepatitis

Shibin Ding, Lanlan Yu, Baijie An, Guofu Zhang, Pengxin Yu, Zhe Wang
BACKGROUND: Hepatic fibrosis, characterized by an excessive accumulation of extracellular matrix, is associated with toxic substance exposure, chronic infections, mechanical injury, airborne fine particulate matter (PM2.5 ) exposure and metabolic disease. This study aimed to investigate the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on hepatic fibrosis and further explored whether combination treatment of PM exposure and high-fat diet (HFD) aggravate the adverse effects in mice...
February 14, 2018: Chemosphere
Eszter Regős, Hadeer Hesham Abdelfattah, Andrea Reszegi, László Szilák, Klára Werling, Gábor Szabó, András Kiss, Zsuzsa Schaff, Ilona Kovalszky, Kornélia Baghy
Increased expression of syndecan-1 is a characteristic feature of human liver cirrhosis. However, no data are available on the significance of this alteration. To address this question we designed a transgenic mouse strain that driven by albumin promoter, expresses human syndecan-1 in the hepatocytes. Liver cirrhosis was induced by thioacetamide in wild type and hSDC1+/+ mice of the identical strain. The process of fibrogenesis, changes in signal transduction and proteoglycan expression were followed. In an in vitro experiment, the effect of syndecan-1 overexpression on the action of TGFβ1 was determined...
February 15, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Yoon Ok Jang, Sung Hoon Kim, Mee-Yon Cho, Kyung Sik Kim, Kyu-Sang Park, Seung-Kuy Cha, Moon Young Kim, Sei Jin Chang, Soon Koo Baik
The beneficial effects of simvastatin on fibrosis in various organs have been reported. In addition, bone marrow (BM)-derived mesenchymal stem cells (MSCs) have been suggested as an effective therapy for hepatic fibrosis and cirrhosis. Recent evidence suggests that pharmacological treatment devoted to regulating stem cell function is a potential new therapeutic strategy that is drawing nearer to clinical practice. The aim of this study was to determine whether the combination treatment of simvastatin plus MSCs (Sim-MSCs) could have a synergistic effect on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model and hepatic stellate cells (HSCs)...
February 8, 2018: Biochemical and Biophysical Research Communications
Haijie Li, Jingqin Lan, Caishun Han, Kaixuan Guo, Guihua Wang, Junbo Hu, Jianping Gong, Xuelai Luo, Zhixin Cao
Liver fibrosis, an important health concern associated to chronic liver injury that provides a permissive environment for cancer development, is characterized by the persistent deposition of extracellular matrix components mainly derived from activated hepatic stellate cells (HSCs). Brg1, the core subunit of the SWI/SNF chromatin remodeling complex, has been proved to associated with nonalcoholic steatohepatitis which may progress to cirrhosis. Herein, we determined whether Brg1 regulates liver fibrosis and examined its mechanism by focusing on HSCs activation...
February 7, 2018: Experimental Cell Research
Cynthia de la Fuente, Chelsea Pinkham, Deemah Dabbagh, Brett Beitzel, Aura Garrison, Gustavo Palacios, Kimberley Alex Hodge, Emanuel F Petricoin, Connie Schmaljohn, Catherine E Campbell, Aarthi Narayanan, Kylene Kehn-Hall
Rift Valley fever virus (RVFV) infects both ruminants and humans leading to a wide variance of pathologies dependent on host background and age. Utilizing a targeted reverse phase protein array (RPPA) to define changes in signaling cascades after in vitro infection of human cells with virulent and attenuated RVFV strains, we observed high phosphorylation of Smad transcription factors. This evolutionarily conserved family is phosphorylated by and transduces the activation of TGF-β superfamily receptors. Moreover, we observed that phosphorylation of Smad proteins required active RVFV replication and loss of NSs impaired this activation, further corroborating the RPPA results...
2018: PloS One
Cheng Chi, Xiao-Ya Liu, Fei Hou, Xiao-Zheng Yu, Chun-Yun Li, Li-Jian Cui, Rui-Xia Liu, Cheng-Hong Yin
BACKGROUND: This study was to evaluate the effects of herbal compound 861 (Cpd861) on ski-related novel protein N (SnoN) and transforming growth factor-β1 (TGF-β1) /Smad signaling in rats with bile duct ligation (BDL)-induced hepatic fibrosis, and to explore the mechanisms of Cpd861 on hepatic fibrosis. METHODS: Thirty Wistar male rats were randomly divided into three groups: sham operation, BDL, and Cpd861. To induce hepatic fibrosis, BDL and Cpd861 group rats underwent bile duct ligation...
February 5, 2018: BMC Complementary and Alternative Medicine
Nannan Pang, Fengbo Zhang, Shaoyu Li, Yuejie Zhu, Chuntao Zhang, Mengting An, Hongying Wang, Wulamu Mamuti, Jianbing Ding, Haining Fan
OBJECTIVES: Cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus (Eg) infection. Th9 cells are reported to be involved in the immune responses in CE patients. This study aims to investigate the role of TGF-β/Smad pathway in the regulation of Th9 cells in CE patients. METHODS: Using Western blot analysis, flow cytometry, qPCR, immunohistochemistry, ELISA and MTT assay, we measured the expression levels of TGF-β/Smad, PU.1, IRF-4, and IL-9 in CE patients...
January 29, 2018: Journal of Infection
Fayang Zhou, Anqi Wang, Dan Li, Yitao Wang, Ligen Lin
The inactivation of hepatic stellate cells (HSCs) has been verified to be an effective therapeutic strategy for treatment of liver fibrosis. Penthorum chinense Pursh has been widely used to protect liver in China; while, the role of P. chinense Pursh in treatment of liver fibrosis is still unexplored. In the current study, the aqueous extract of P. chinense Pursh (PCE) was found to suppress the expressions of fibrotic markers, including collagen I and α-smooth muscle actin (α-SMA), in human HSCs (LX-2); and its major active constituent, pinocembrin (PIN), was discovered to inhibit the expressions of fibrotic markers in LX-2 cells and rat HSCs (HSC-T6)...
January 15, 2018: Toxicology and Applied Pharmacology
Zhichao Dong, Qi Gao, Hao Guo
Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid isolated from Rabdosia japonica var. glaucocalyx. A large number of studies have shown that GLA possesses important pharmacological activities, such as anti-inflammatory, antitumor, antifibrosis, and antiplatelet activities. However, the role of GLA in the pathogenesis of liver fibrosis remains undefined. Therefore, the aim of this study was to investigate the effects of GLA on hepatic stellate cells (HSCs) activation/proliferation and migration in vitro and its possible mechanism in liver fibrosis...
January 12, 2018: DNA and Cell Biology
Rachel Harrington-Kandt, Elena Stylianou, Lucy A Eddowes, Pei Jin Lim, Lisa Stockdale, Nawamin Pinpathomrat, Naomi Bull, Janet Pasricha, Marta Ulaszewska, Yulia Beglov, Sophie Vaulont, Hal Drakesmith, Helen McShane
Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection...
2018: PloS One
Fei Hou, Ruixia Liu, Xiaoya Liu, Lijian Cui, Xiaozheng Yu, Yan Wen, Huiguo Ding, Chenghong Yin
Arkadia is able to degrade key signaling molecules in the transforming growth factor (TGF)‑β1 signaling pathway; however, the expression of Arkadia in the liver during development and progression of TGF‑β1/Smad signaling‑regulated hepatic fibrosis remains to be elucidated. The present study aimed to examine Arkadia expression in the livers of two rat models of hepatic fibrosis induced by bile duct ligation and carbon tetrachloride intoxication, and in human liver samples from patients with hepatic fibrosis...
December 22, 2017: International Journal of Molecular Medicine
Peng Li, Yongyun Li, Liqi Zhu, Zhi Yang, Jie He, Lihua Wang, Qingfeng Shang, Hui Pan, Huixue Wang, Xiong Ma, Bin Li, Xianqun Fan, Shengfang Ge, Renbing Jia, He Zhang
Liver fibrosis is overly exuberant wound healing that leads to portal hypertension or liver cirrhosis. Recent studies have demonstrated the functions of bone morphogenetic protein 9 (BMP9) in liver fibrosis, and thus, targeting liver-specific BMP9 abnormalities will become an attractive approach for developing therapeutics to treat liver fibrosis. Here, we reveal that BMP9 serves as a valuable serum diagnostic indicator and efficient therapeutic target to attenuate liver fibrogenesis. Our analysis of biopsies from liver fibrotic patients revealed that higher BMP9 levels accompanied advanced stages of liver fibrosis...
March 2018: Biochimica et Biophysica Acta
Jie Chen, Detian Li
Renal fibrosis yields decreased renal function and is a potent contributor to chronic kidney disease (CKD). Telbivudine (LdT) is an anti-hepatitis B virus (HBV) drug that has been found to steadily improve renal function, but the mechanism of drug action is unclear. One explanation is that LdT impacts inflammatory or fibrotic pathways. In this study, we investigated renal protection by LdT in a rat model of unilateral ureteral obstruction (UUO). UUO rats received oral gavage of LdT (1, 1.5, or 2g/kg/day) for 5weeks...
February 2018: International Immunopharmacology
Courtney E Morgan, Neel A Mansukhani, Mark K Eskandari, Heron E Rodriguez
OBJECTIVE: Isolated spontaneous dissection of the superior mesenteric artery (SMA) and celiac artery (CA) remains a rare condition; however, it has been increasingly noted incidentally on diagnostic imaging. The purpose of this study was to examine the natural history and outcomes of patients presenting with isolated spontaneous mesenteric artery dissection (SMAD). We hypothesized that most SMADs can be treated nonoperatively. METHODS: This was a single-center retrospective review of patients presenting with the diagnosis of SMAD between 2006 and 2016...
November 13, 2017: Journal of Vascular Surgery
Yu Cai, Guanqun Huang, Lijie Ma, Ling Dong, She Chen, Xizhong Shen, Shuncai Zhang, Ruyi Xue, Deqiang Sun, Si Zhang
We previously reported that Smad ubiquitin regulatory factor 2 (Smurf2) activity was decreased in human fibrotic livers. Here, we overexpressed Smurf2 in livers of transgenic mice and observed inhibited collagen deposition and hepatic stellate cell activation in fibrotic model induced by carbon tetrachloride treatment or bile duct ligation. Hepatic Smurf2 overexpression also inhibited the production of connective tissue growth factor (CTGF), a central mediator of liver fibrosis. Using miRNA array and bioinformatics analyses, we identified miR-132 as a mediator of this inhibitory effect...
February 2018: Biochimica et Biophysica Acta
Fujun Yu, BiCheng Chen, XuFei Fan, Guojun Li, Peihong Dong, Jianjian Zheng
BACKGROUND/AIMS: Recently, microRNAs (miRNAs) have been demonstrated to act as regulators of activation of hepatic stellate cells (HSCs). It is well known that the main profibrogenic inducer transforming growth factor-β1 (TGF-β1) contributes to HSC activation, which is a key event in liver fibrosis. Increasing studies show that miR-9-5p is down-regulated in liver fibrosis and restoration of miR-9-5p limits HSC activation. However, the role of miR-9-5p in TGF-β1-induced HSC activation is still not clear...
October 27, 2017: Cellular Physiology and Biochemistry
Hyuk Moon, Kwang-Hyub Han, Simon Weonsang Ro
Many studies have focused on the tumor suppressive role of TGF-β signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of TGF-β inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, TGF-β inhibition consistently suppressed hepatic tumorigenesis that was induced either by activated RAS plus p53 downregulation or by the co-activation of RAS and TAZ signaling; this demonstrates the requirements for canonical TGF-β signaling in tumorigenesis...
October 25, 2017: BMB Reports
Y P Mu, X Zhang, W W Fan, X W Li, G F Chen, J M Chen, H Zhang, P Liu
Objective: The Notch signaling pathway is closely related to biliary fibrosis. Previous studies have shown that Astragaloside (AS) can prevent the progression of cholestatic liver fibrosis. The purpose of this study is to observe the effect of AS on the regulation of Notch signaling pathway in biliary fibrosis. Methods: Cholestatic liver fibrosis was established by common bile duct ligation (BDL) in rats. Two weeks after BDL, the rats were randomly divided into a model group (i.e., BDL), an Astragalosides group (AS), and a sorafenib (SORA) positive control group and treated for 3 weeks...
August 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Jianlin He, Kaikai Bai, Bihong Hong, Feng Zhang, Shizhong Zheng
Fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has been reported to exert beneficial health effects, including hepatoprotection. However, the effect of DHA alone has not been well studied, and the mechanism is not fully understood. In the present study, we reported the protective effect of DHA on carbon tetrachloride (CCl4) induced hepatic fibrosis. Compared with the control group, the CCl4 group showed hepatic damage as evidenced by histological changes and elevation in serum transaminase activity, fibrosis, inflammation and oxidative stress levels...
October 13, 2017: International Immunopharmacology
Chloé Latour, Céline Besson-Fournier, Ophélie Gourbeyre, Delphine Meynard, Marie-Paule Roth, Hélène Coppin
Lack of either BMP6 or the BMP co-receptor hemojuvelin (HJV) in mice leads to a similar phenotype with hepcidin insufficiency, hepatic iron loading, and extrahepatic iron accumulation in males. This is consistent with the current views that HJV is a co-receptor for BMP6 in hepatocytes. To determine whether BMP6 and HJV may also signal to hepcidin independently of each other, we intercrossed Hjv(-/-) and Bmp6(-/-) mice and compared the phenotype of animals of the F2 progeny. Loss of Bmp6 further repressed Smad signaling and hepcidin expression in the liver of Hjv(-/-) mice of both genders, and led to iron accumulation in the pancreas and the heart of females...
October 11, 2017: Blood
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