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Smad AND Hepatitis

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https://www.readbyqxmd.com/read/29327938/glaucocalyxin-a-attenuates-the-activation-of-hepatic-stellate-cells-through-the-tgf-%C3%AE-1-smad-signaling-pathway
#1
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
https://www.readbyqxmd.com/read/29324800/hepcidin-deficiency-and-iron-deficiency-do-not-alter-tuberculosis-susceptibility-in-a-murine-m-tb-infection-model
#2
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
#3
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
https://www.readbyqxmd.com/read/29223735/targeting-secreted-cytokine-bmp9-gates-the-attenuation-of-hepatic-fibrosis
#4
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...
December 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29207359/telbivudine-attenuates-uuo-induced-renal-fibrosis-via-tgf-%C3%AE-smad-and-nf-%C3%AE%C2%BAb-signaling
#5
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...
December 2, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29146096/ten-year-review-of-isolated-spontaneous-mesenteric-arterial-dissections
#6
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
https://www.readbyqxmd.com/read/29100790/smurf2-an-e3-ubiquitin-ligase-interacts-with-pde4b-and-attenuates-liver-fibrosis-through-mir-132-mediated-ctgf-inhibition
#7
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...
October 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29073595/epigenetically-regulated-microrna-9-5p-suppresses-the-activation-of-hepatic-stellate-cells-via-tgfbr1-and-tgfbr2
#8
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
https://www.readbyqxmd.com/read/29065973/pro-tumorigenic-roles-of-tgf-%C3%AE-signaling-during-the-early-stages-of-liver-tumorigenesis-through-upregulation-of-snail
#9
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
https://www.readbyqxmd.com/read/29056006/-mechanism-of-astragaloside-prevents-cholestatic-liver-fibrosis-through-inhibition-of-notch-signaling-activation
#10
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
https://www.readbyqxmd.com/read/29035816/docosahexaenoic-acid-attenuates-carbon-tetrachloride-induced-hepatic-fibrosis-in-rats
#11
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
https://www.readbyqxmd.com/read/29021231/deletion-of-bmp6-worsens-the-phenotype-of-hjv-deficient-mice-and-attenuates-hepcidin-levels-reached-after-lps-challenge
#12
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
https://www.readbyqxmd.com/read/28992660/alpha-mangostin-inhibits-hepatic-stellate-cells-activation-through-tgf-%C3%AE-smad-and-akt-signaling-pathways-an-in-vitro-study-in-lx2
#13
Rahmaniah Rahmaniah, Yuyuntia Yuyuntia, Vivian Soetikno, Wawaimuli Arozal, Radiana Dhewayani Antarianto, Melva Louisa
Background Alpha mangostin has been reported to have activity for the treatment of liver fibrosis in the rats. However, the mechanisms of action are poorly understood. This study was aimed to investigate the effect of alpha mangostin on hepatic stellate cells (HSC) activation and proliferation through TGF-β/Smad and Akt signaling pathways. Methods Immortalized HSC, LX2 cells, were incubated with TGF-β with or without alpha mangostin (5 or 10 μM). Sorafenib 10 µM was used as positive control. LX2 viability was counted using trypan blue exclusion method...
October 9, 2017: Drug Research
https://www.readbyqxmd.com/read/28971221/uncoupled-iron-homeostasis-in-type-2-diabetes-mellitus
#14
Sandro Altamura, Stefan Kopf, Julia Schmidt, Katja Müdder, Ana Rita da Silva, Peter Nawroth, Martina U Muckenthaler
Diabetes mellitus is frequently associated with iron overload conditions, such as primary and secondary hemochromatosis. Conversely, patients affected by type 2 diabetes mellitus (T2DM) show elevated ferritin levels, a biomarker for increased body iron stores. Despite these documented associations between dysregulated iron metabolism and T2DM, the underlying mechanisms are poorly understood. Here, we show that T2DM patients have reduced serum levels of hepcidin, the iron-regulated hormone that maintains systemic iron homeostasis...
December 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28962196/smad7-overexpressing-rat-bmscs-inhibit-the-fibrosis-of-hepatic-stellate-cells-by-regulating-the-tgf-%C3%AE-1-smad-signaling-pathway
#15
Shi-Pin Wu, Zhi Yang, Fu-Rong Li, Xiao-Di Liu, Hong-Tao Chen, Dong-Na Su
Mesenchymal stem cells (MSCs) are able to differentiate into hepatocytes, promote the regeneration of hepatic cells and inhibit the progression of hepatic fibrosis. Transforming growth factor (TGF)-β1 is one of the key factors in the development of liver fibrosis, which also promotes extracellular matrix (ECM) formation. Drosophila mothers against decapentaplegic 7 (Smad7) is an essential negative regulator in the TGF-β1/Smad signaling pathway. In the present study, bone mesenchymal stem cells (BMSCs) were isolated from rat bone marrow and transfected with lentiviral vectors carrying the Smad7 gene...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28936800/evodiamine-ameliorates-liver-fibrosis-in-rats-via-tgf-%C3%AE-1-smad-signaling-pathway
#16
Dongmei Yang, Li Li, Shanjun Qian, Lixin Liu
Liver fibrosis is considered to be a result of chronic liver pathological changes, and hepatic stellate cells (HSCs) play an important role during this process. Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities. This study focused on the effects of evodiamine on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and HSCs in vitro via the TGF-β1/Smad signaling pathway. A liver fibrosis rat model was established by the intraperitoneal injection of CCl4 (3 ml/kg, 30% in olive oil)...
September 21, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28929107/microrna-195-activates-hepatic-stellate-cells-in-vitro-by-targeting-smad7
#17
Li-Ying Song, Yu-Tao Ma, Cui-Fang Wu, Chun-Jiang Wang, Wei-Jin Fang, Shi-Kun Liu
BACKGROUND AND AIM: Aberrant activation of the TGF-β1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs. The aim of this study was to investigate the role of miRNA-195 in HSCs activation. METHODS: A liver fibrotic rat model induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195. The expression levels of miR-195, Smad7, and α-SMA in HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28918026/anti-fibrotic-effects-of-synthetic-oligodeoxynucleotide-for-tgf-%C3%AE-1-and-smad-in-an-animal-model-of-liver-cirrhosis
#18
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Mi-Gyeong Gwon, Hyemin Gu, Yoon-Yub Park, Kwan-Kyu Park
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28915589/casticin-attenuates-liver-fibrosis-and-hepatic-stellate-cell-activation-by-blocking-tgf-%C3%AE-smad-signaling-pathway
#19
Ling Zhou, Xiaoying Dong, Linlin Wang, Lanlan Shan, Ting Li, Wanfu Xu, Yan Ding, Mingqiang Lai, Xiaojun Lin, Meng Dai, Xiaochun Bai, Chunhong Jia, Hang Zheng
Although many advances have been made in understanding the pathogenesis of liver fibrosis, few options are available for treatment. Casticin, one of the major flavonoids in Fructus Viticis extracts, has shown hepatoprotective potential, but its effects on liver fibrosis are not clear. In this study, we investigated the antifibrotic activity of casticin and its underlying mechanism in vivo and in vitro. Male mice were injected intraperitoneally with carbon tetrachloride (CCl4) or underwent bile duct ligation (BDL) to induce liver fibrosis, followed by treatment with casticin or vehicle...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893916/the-role-of-activins-in-hepcidin-regulation-during-malaria
#20
Natasha Spottiswoode, Andrew E Armitage, Andrew R Williams, Alex J Fyfe, Sumi Biswas, Susanne H Hodgson, David Llewellyn, Prateek Choudhary, Simon J Draper, Patrick Duffy, Hal Drakesmith
Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in Plasmodium berghei murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation...
September 11, 2017: Infection and Immunity
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