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Smad AND Hepatitis

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https://www.readbyqxmd.com/read/29789425/a-heterodimer-formed-by-bone-morphogenetic-protein-9-bmp9-and-bmp10-provides-most-bmp-biological-activity-in-plasma
#1
Emmanuelle Tillet, Marie Ouarné, Agnès Desroches-Castan, Christine Mallet, Mariela Subileau, Robin Didier, Anna Lioutsko, Guillaume Belthier, Jean-Jacques Feige, Sabine Bailly
Bone morphogenetic protein 9 (BMP9) and BMP10 are the two high-affinity ligands for the endothelial receptor activin receptor-like kinase 1 (ALK1) and are key regulators of vascular remodeling. They are both present in the blood, but their respective biological activities are still a matter of debate. The aim of the present work was to characterize their circulating forms to better understand how their activities are regulated in vivo. First, by cotransfecting BMP9 and BMP10, we found that both can form a disulfide-bonded heterodimer in vitro and that this heterodimer is functional on endothelial cells via ALK1...
May 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29785090/semen-brassicae-ameliorates-hepatic-fibrosis-by-regulating-transforming-growth-factor-%C3%AE-1-smad-nuclear-factor-%C3%AE%C2%BAb-and-akt-signaling-pathways-in-rats
#2
Si Cao, Baoping Zheng, Tao Chen, Xinfeng Chang, Bao Yin, Zhihua Huang, Ping Shuai, Limin Han
Purpose: There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. Methods: Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL·kg-1 ) at a dose of 200 mg·kg-1 twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29729074/liver-regeneration-accelerates-hepatitis-b-virus-related-tumorigenesis-of-hepatocellular-carcinoma
#3
Chiao-Fang Teng, Hong-Yi Chang, Hung-Wen Tsai, Wen-Chuan Hsieh, Yu-Hao Kuo, Ih-Jen Su, Yih-Jyh Lin
Although partial hepatectomy (PH) to remove tumors provides a potential cure of hepatocellular carcinoma (HCC), long-term survival of hepatitis B virus (HBV)-related HCC patients after PH remains a big challenge. Early recurrence within two years post-PH is associated with the dissemination of primary HCC. However, late recurrence after two years post-PH is supposed due to the de novo or a secondary tumor. Since PH initiates liver regeneration (LR), we hypothesize that LR may accelerate tumorigenesis through activation of pre-existing precancerous lesions in the remaining liver...
May 4, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29701195/-yap-taz-regulates-multiple-signal-pathways-in-the-genesis-and-development-of-hepatic-fibrosis
#4
Huozhen Pan, Ming Liao, Pengshu Song
Hepatic fibrosis is a repair response to liver injury, and hepatic stellate cell activation is the center of hepatic fibrosis, which involves Hippo, Notch, Wnt/β-catenin, and TGF-β/Smad signaling pathways. YAP/TAZ is an important nucleus factor for Hippo tumor suppressor pathway and its activity is the key to the growth of whole organs, cell proliferation, and specific amplification of progenitor cells in the process of tissue renewal and regeneration. As the hub of signaling pathways, such as Hippo, Notch, Wnt/β-catenin, TGF-β/Smad signaling, YAP/TAZ regulates the genesis and development of liver fibrosis...
March 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29684485/dysregulation-of-fibrosis-related-genes-in-hcv-induced-liver-disease
#5
Reham M Dawood, Mai Abd El-Meguid, Marwa K Ibrahim, Noha G Bader El Din, Ahmed Barakat, Khaled El-Wakeel, Mohamed Darwish Ahmed Abd Alla, George Y Wu, Mostafa K El Awady
BACKGROUND: Liver fibrosis results from a wound healing response to chronic injury, which leads to excessive matrix deposition. Genome wide association studies have showen transcriptional dysregulation in mild and severe liver fibrosis. Recent studies suggested that genetic markers may be able to define the exact stage of liver fibrosis. AIM: To define genes or genetic pathways that could serve as markers for staging or as therapeutic targets to halt progression of liver fibrosis...
April 20, 2018: Gene
https://www.readbyqxmd.com/read/29609638/the-truncated-mutant-hbsag-expression-increases-the-tumorigenesis-of-hepatitis-b-virus-by-regulating-tgf-%C3%AE-smad-signaling-pathway
#6
Meng-Lan Wang, Dong-Bo Wu, Ya-Chao Tao, Lan-Lan Chen, Cui-Ping Liu, En-Qiang Chen, Hong Tang
BACKGROUND: It has been reported that the emergence of HBV rtA181T/sW172* mutant could result in a dominant secretion defect of HBsAg and increase the risk of HCC development. This study was designed to reveal the role and possible pathogenic mechanism of truncated mutant HBsAg in tumorigenesis of HBV rtA181T/sW172* mutant. RESULTS: As compared to wide type or substituted mutant HBsAg, the ratio of cell clones was significant higher in L02 cells stable expressing truncated mutant HBsAg...
April 2, 2018: Virology Journal
https://www.readbyqxmd.com/read/29601129/effect-of-histone-deacetylase-inhibitor-on-epithelial-mesenchymal-transition-of-liver-fibrosis
#7
Maggie M Ramzy, Hend M Abdelghany, Nagwa M Zenhom, Nashwa F El-Tahawy
Liver fibrosis is an excessively reversible wound healing process and the fibrotic disorder is the activation of hepatic stellate cell that requires extensive alterations in gene expression. As reversible deacetylation of histone proteins modulate gene expression, we examined the effect of valproic acid (VPA) as selective histone deacetylase inhibitor on CCl-4 induced liver fibrosis. Thirty rats were divided into three equal groups; control group, fibrotic group and VPA-treated group. The rats were sacrificed after 6 weeks of liver fibrosis induction...
March 30, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29600572/adenine-alleviates-iron-overload-by-camp-pka-mediated-hepatic-hepcidin-in-mice
#8
Yingqi Zhang, Xudong Wang, Qian Wu, Hao Wang, Lu Zhao, Xinhui Wang, Mingdao Mu, Enjun Xie, Xuyan He, Dandan Shao, Yanna Shang, Yongrong Lai, Yelena Ginzburg, Junxia Min, Fudi Wang
Hemochromatosis is prevalent and often associated with high rates of morbidity and mortality worldwide. The safe alternative iron-reducing approaches are urgently needed in order to better control iron overload. Our unbiased vitamin screen for modulators of hepcidin, a master iron regulatory hormone, identifies adenine (vitamin B4) as a potent hepcidin agonist. Adenine significantly induced hepcidin mRNA level and promoter activity activation in human cell lines, possibly through BMP/SMAD pathway. Further studies in mice validated the effect of adenine on hepcidin upregulation...
March 30, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29544731/autocrine-transforming-growth-factor-%C3%AE-activin-a-smad-signaling-induces-hepatic-progenitor-cells-undergoing-partial-epithelial-mesenchymal-transition-states
#9
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
May 2018: Biochimie
https://www.readbyqxmd.com/read/29455124/combination-effects-of-airborne-particulate-matter-exposure-and-high-fat-diet-on-hepatic-fibrosis-through-regulating-the-ros-endoplasmic-reticulum-stress-tgf%C3%AE-smads-axis-in-mice
#10
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...
May 2018: Chemosphere
https://www.readbyqxmd.com/read/29454902/syndecan-1-inhibits-early-stages-of-liver-fibrogenesis-by-interfering-with-tgf%C3%AE-1-action-and-upregulating-mmp14
#11
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 16, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29428718/synergistic-effects-of-simvastatin-and-bone-marrow-derived-mesenchymal-stem-cells-on-hepatic-fibrosis
#12
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 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29427621/brg1-promotes-liver-fibrosis-via-activation-of-hepatic-stellate-cells
#13
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...
March 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29408900/phosphoproteomic-analysis-reveals-smad-protein-family-activation-following-rift-valley-fever-virus-infection
#14
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
https://www.readbyqxmd.com/read/29402324/herbal-compound-861-prevents-hepatic-fibrosis-by-inhibiting-the-tgf-%C3%AE-1-smad-snon-pathway-in-bile-duct-ligated-rats
#15
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
https://www.readbyqxmd.com/read/29391143/tgf-%C3%AE-smad-signaling-pathway-positively-up-regulates-the-differentiation-of-interleukin-9-producing-cd4-t-cells-in-human-echinococcus-granulosus-infection
#16
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...
April 2018: Journal of Infection
https://www.readbyqxmd.com/read/29352975/pinocembrin-from-penthorum-chinense-pursh-suppresses-hepatic-stellate-cells-activation-through-a-unified-sirt3-tgf-%C3%AE-smad-signaling-pathway
#17
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)...
February 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29327938/glaucocalyxin-a-attenuates-the-activation-of-hepatic-stellate-cells-through-the-tgf-%C3%AE-1-smad-signaling-pathway
#18
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...
March 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29324800/hepcidin-deficiency-and-iron-deficiency-do-not-alter-tuberculosis-susceptibility-in-a-murine-m-tb-infection-model
#19
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
https://www.readbyqxmd.com/read/29286088/arkadia-protein-expression-is-reduced-in-the-liver-during-the-progression-of-hepatic-fibrosis
#20
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...
March 2018: International Journal of Molecular Medicine
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