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https://www.readbyqxmd.com/read/28647409/a-residue-specific-insight-into-the-arkadia-e3-ubiquitin-ligase-activity-and-conformational-plasticity
#1
Maria Birkou, Christos T Chasapis, Konstantinos D Marousis, Ariadni K Loutsidou, Detlef Bentrop, Moreno Lelli, Torsten Herrmann, Jonathon M Carthy, Vasso Episkopou, Georgios A Spyroulias
Arkadia (Rnf111) is an E3 Ubiquitin ligase that plays a central role in the amplification of TGF-β signaling responses by targeting for degradation the negative regulators of the pathway, Smad6 and Smad7 and the nuclear co-repressors Ski and Skil (SnoN). Arkadia's function in vivo depends on the RING-H2 interaction with the E2 enzyme UbcH5b in order to ligate ubiquitin chains on its substrates. A conserved tryptophan (W972) in the C-terminal α-helix is widely accepted as essential for E2 recruitment and interaction and thus also for E3 enzymatic activity...
June 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28646304/ndrg2-knockdown-promotes-fibrosis-in-renal-tubular-epithelial-cells-through-tgf-%C3%AE-1-smad3-pathway
#2
Zhibo Jin, Chaohui Gu, Fengyan Tian, Zhankui Jia, Jinjian Yang
Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-β1-induced renal tubular epithelial cells (HK-2)...
June 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28638433/shenqiwan-ameliorates-renal-fibrosis-in-rats-by-inhibiting-tgf-%C3%AE-1-smads-signaling-pathway
#3
Hongshu Chen, Yiqing Xu, Yuanxiao Yang, Xiaojie Zhou, Shijie Dai, Changyu Li
Epithelial-mesenchymal transition (EMT) refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF). Traditional Chinese Medicine Shenqiwan (SQW) is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg) was established and intragastrically treated with various concentrations of SQW at dose of 1...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28633927/dencichine-ameliorates-kidney-injury-in-induced-type-ii-diabetic-nephropathy-via-the-tgf-%C3%AE-smad-signalling-pathway
#4
Li Jie, Qiu Pengcheng, He Qiaoyan, Bi Linlin, Zhang Meng, Wang Fang, Jia Min, Yan Li, Zhang Ya, Yang Qian, Wang Siwang
Diabetic nephropathy (DN), a common complication associated with both type I and type II diabetes mellitus (DM), is a major cause of chronic nephropathy and a common cause of end-stage renal diseases (ESRD) throughout the world. This study is aimed to determine whether dencichine (De) can ameliorate renal damage in high-glucose-and-fat diet combined STZ (streptozocin) induced DN in type II DM rats and to investigate the potential underlying mechanisms. Markers of metabolism, diabetes, and renal function, and levels of extracellular matrix (ECM) collagen I (Col I), collagen IV (Col IV), fibronectin (FN) and laminin (LN), and of proteins in the TGF-β/Smad pathway were analysed through RT-PCR, western blot, immunofluorescence and immunohistochemistry...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28630605/xinfuli-granule-improves-post-myocardial-infarction-ventricular-remodeling-and-myocardial-fibrosis-in-rats-by-regulating-tgf-%C3%AE-smads-signaling-pathway
#5
Jie Ma, Zhi-Yuan Li, Xiao-Peng Liang, Cai-Xia Guo, Pei-Pei Lu, Li-Hong Ma
BACKGROUND: Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI). METHODS: Sprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to five groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM)...
May 2017: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28622443/mir-2909-regulates-isgylation-system-via-stat1-signalling-through-negative-regulation-of-socs3-in-prostate-cancer
#6
Shiekh Gazalla Ayub, Deepak Kaul
One of the well-document strategies adopted by tumour cells for progression is to evade immune surveillance mechanisms. An understanding of the tight interaction between immunity and progression of cancer can provide novel treatment options for different malignancies including prostate cancer (PCa). Here, we have shown that AATF genome encoded miR-2909, known to play role both in immunity and cancer upregulates various interferon stimulating genes (ISGs) including ISGylation system through STAT1. Our results revealed that miR-2909 up-regulates STAT1 through negative regulation of SOCS3 and not through up-regulation of Type 1 interferon (IFN) production...
June 16, 2017: Andrology
https://www.readbyqxmd.com/read/28606878/resolution-of-inflammation-in-inflammatory-bowel-disease
#7
REVIEW
Gerhard Rogler
Treatment of inflammatory bowel disease at present mainly targets mediators of inflammation to stop or suppress pro-inflammatory processes. Typical examples are steroids, suppression of T cells by thioguanine nucleotides, or antibodies against cytokines such as tumour necrosis factor, interleukin 12, or interleukin 23. In addition to suppression of inflammation, development of therapeutic strategies that support resolution of inflammation or that actively resolve inflammation might be desirable. Resolution of inflammation is now seen as an active process involving specific mediators (eg, lipid mediators or specific cytokines) that is mandatory to restore organ function and completely shut down inflammation...
July 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28601662/inhibition-of-mir-32-activity-promoted-emt-induced-by-pm2-5-exposure-through-the-modulation-of-the-smad1-mediated-signaling-pathways-in-lung-cancer-cells
#8
Dan Yang, Mingyue Ma, Weiqiang Zhou, Biao Yang, Chunling Xiao
Epithelial mesenchymal transition (EMT) is a crucial morphological event during tumor progression. The present study reported that EMT could be triggered by airborne fine particulate matter (PM) with a mean diameter of less than 2.5 μm (PM2.5) in human lung cancer cells. We also aimed to elucidate the possible mechanisms of these processes. The results showed that treatment with PM2.5 promoted the activity of the SMAD family member 1 (Smad1)-mediated signaling pathway and downregulated the expression of the inhibitory Smad proteins Smad6 and Smad7 in lung cancer cells...
May 30, 2017: Chemosphere
https://www.readbyqxmd.com/read/28597341/in-silico-prediction-and-validation-of-gfap-as-an-mir-3099-target-in-mouse-brain
#9
Shahidee Zainal Abidin, Jia-Wen Leong, Marzieh Mahmoudi, Norshariza Nordin, Syahril Abdullah, Pike-See Cheah, King-Hwa Ling
MicroRNAs are small non-coding RNAs that play crucial roles in the regulation of gene expression and protein synthesis during brain development. MiR-3099 is highly expressed throughout embryogenesis, especially in the developing central nervous system. Moreover, miR-3099 is also expressed at a higher level in differentiating neurons in vitro, suggesting that it is a potential regulator during neuronal cell development. This study aimed to predict the target genes of miR-3099 via in-silico analysis using four independent prediction algorithms (miRDB, miRanda, TargetScan, and DIANA-micro-T-CDS) with emphasis on target genes related to brain development and function...
June 8, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28580633/smad7-positively-regulates-keratinocyte-proliferation-in-psoriasis
#10
D Di Fusco, F Laudisi, V Dinallo, I Monteleone, A Di Grazia, I Marafini, E Troncone, A Colantoni, A Ortenzi, C Stolfi, M Picardo, G Monteleone
BACKGROUND: Transforming growth factor (TGF)-β1 exerts inhibitory effects on keratinocyte proliferation. OBJECTIVES: To examine whether Smad7, a known inhibitor of TGF-β1 signalling, is involved in the psoriasis-associated keratinocyte hyper-proliferation. METHODS: Smad7 was evaluated in skin sections of psoriatic patients and healthy controls and in mice with Aldara-induced skin pathology by real-time PCR and immunohistochemistry. To assess whether Smad7 positively regulates the in vivo keratinocyte growth, mice treated with Aldara received daily cutaneous administration of Smad7 antisense oligonucleotide (AS)...
June 5, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28571007/eplerenone-prevents-atrial-fibrosis-via-the-tgf-%C3%AE-signaling-pathway
#11
Lili Du, Mu Qin, Yi Yi, Xiaoqing Chen, Weifeng Jiang, Li Zhou, Daoliang Zhang, Kai Xu, Yiqing Yang, Chao Li, Yan Liu, Xu Liu, Sheng-Zhong Duan
OBJECTIVES: Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms. METHODS: EPL-treated MHC-TGFcys33ser transgenic mice that have selective atrial fibrosis (Tx+EPL mice), as well as control mice, were used for in vivo studies including histological analyses, Western blotting, and qRT-PCR studies...
June 2, 2017: Cardiology
https://www.readbyqxmd.com/read/28566468/smad7-protects-against-acute-kidney-injury-by-rescuing-tubular-epithelial-cells-from-the-g1-cell-cycle-arrest
#12
Sha Fu, Ying Tang, Xiao Ru Huang, Min Feng, Anping Xu, Hui Y Lan
Smad7 plays a protective role in chronic kidney disease; however, its role in acute kidney injury (AKI) remains unexplored. Here we report that Smad7 protects against AKI by rescuing the G1 cell cycle arrest of tubular epithelial cells (TECs) in ischemia/reperfusion-induced AKI in mice in which Smad7 gene is disrupted or restored locally into the kidney. In Smad7 gene knockout (KO) mice, more severe renal impairment including higher levels of serum creatinine and massive tubular necrosis was developed at 48 h after AKI...
May 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28560399/microrna-expression-analysis-during-fk506-induced-osteogenic-differentiation-in-rat-bone-marrow-stromal-cells
#13
Jing Zhang, Xiaoping Yu, Youcheng Yu, Yiming Gong
FK506 (also known as tacrolimus) is a potent immunosuppressive agent that is widely used in the treatment of graft-rejection and autoimmune diseases. FK506 has attracted additional attention owing to its potential role in osteogenic differentiation and bone formation. MicroRNAs (miRNAs) have been demonstrated to serve important roles in the regulation of osteogenic differentiation; however, identification of specific miRNAs and their roles in regulating FK506‑induced osteogenic differentiation have been poorly examined...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28545667/arctigenin-suppresses-renal-interstitial-fibrosis-in-a-rat-model-of-obstructive-nephropathy
#14
Ao Li, Xiaoxun Zhang, Mao Shu, Mingjun Wu, Jun Wang, Jingyao Zhang, Rui Wang, Peng Li, Yitao Wang
BACKGROUND: Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF. PURPOSE: The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28544244/branched-chain-amino-acids-supplementation-modulates-tgf-%C3%AE-1-smad-signaling-pathway-and-interleukins-in-ccl4-induced-liver-fibrosis
#15
Naglaa F Khedr, Eman G Khedr
The alterations and low levels of circulating branched chain amino acids (BCAAs), leucine, isoleucine and valine, are associated with liver diseases. The study was designed to evaluate hepatoprotective effect of BCAAs on CCl4 -induced liver fibrosis and to investigate the molecular mechanisms underlying these effects in rats. Thirty male rats were divided into three groups. Control group (n=10), CCl4 group (n=10); rats were injected with CCl4 (1 mL/kg of 0.5:1 v/v injected i.p. twice weekly for 12 weeks). CCl4 +BCAAs group (n=10); rats were injected with similar doses of CCl4 and supplemented with a mixture of 600 mg/kg BCAAs (2: 1: 1...
May 23, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28543554/smad3-expression-and-regulation-of-fibroplasia-in-vocal-fold-injury
#16
Nao Hiwatashi, Peter A Benedict, Gregory R Dion, Renjie Bing, Iv Kraja, Milan R Amin, Ryan C Branski
OBJECTIVE: Recent reports highlight the efficacy of small interfering RNA (siRNA) targeting SMAD3 to regulate transforming growth factor β (TGF-β)-mediated fibroplasia in vocal fold fibroblasts. The current study sought to investigate SMAD3 expression during wound healing in vivo and quantify the downstream transcriptional events associated with SMAD3 knockdown in vitro. STUDY DESIGN: In vivo and in vitro. METHODS: Unilateral vocal fold injury was created in a rabbit model...
May 20, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28512472/pulsed-electromagnetic-field-regulates-microrna-21-expression-to-activate-tgf-%C3%AE-signaling-in-human-bone-marrow-stromal-cells-to-enhance-osteoblast-differentiation
#17
Nagarajan Selvamurugan, Zhiming He, Daniel Rifkin, Branka Dabovic, Nicola C Partridge
Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs' cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28499242/potential-ameliorative-effects-of-grape-seed-derived-polyphenols-against-cadmium-induced-prostatic-deficits
#18
Yongfang Lei, Qian Chen, Jinglou Chen, Dong Liu
Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study, rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium chlorine (CdCl2) through drinking water for 20 weeks. Grape seed-derived polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic levels of E-cadherin, fibronectin, and α-smooth muscle actin were measured by immunohistochemical and qPCR analysis. The oxidative stress was measured by detecting the levels of malondialdehyde, nitric oxide, reduced glutathione/oxidized glutathione and enzymatic antioxidant status...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28498432/time-%C3%A2-and-oxygen-dependent-expression-and-regulation-of-ndrg1-in-human-brain-cancer-cells
#19
Harun Muayad Said, Roghaiyeh Safari, Ghada Al-Kafaji, Ralf-Ingo Ernestus, Mario Löhr, Astrid Katzer, Michael Flentje, Carsten Hagemann
N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress metastasis, invasion and migration of cancer cells. It is regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation is both induced and controlled by HIF-1α-dependent and -independent pathways under hypoxic conditions. However, there are profound differences in the way NDRG1 expression is regulated by HIF-1α and other transcription factors. Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions...
May 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28494854/yangfei-kongliu-formula-a-compound-chinese-herbal-medicine-combined-with-cisplatin-inhibits-growth-of-lung-cancer-cells-through-transforming-growth-factor-%C3%AE-1-signaling-pathway
#20
Shui-Jie Shen, Yong-Hong Zhang, Xiao-Xia Gu, Shui-Ju Jiang, Ling-Jun Xu
OBJECTIVE: To investigate the tumor inhibition effect of Yangfei Kongliu Formula (YKF), a compound Chinese herbal medicine, combined with cisplatin (DDP) and its action mechanisms. METHODS: C57BL/6 mice with Lewis lung carcinoma were divided into six groups: control group (C), DDP group (2 mg/kg, DDP), low-dose YKF group (2.43 g/kg, L), high-dose YKF group (24.3 g/kg, H), low-dose YKF combined with DDP group (L + DDP) and high-dose YKF combined with DDP group (H + DDP)...
May 2017: Journal of Integrative Medicine
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