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https://www.readbyqxmd.com/read/27920040/regulation-of-tgf-%C3%AE-family-signaling-by-inhibitory-smads
#1
Keiji Miyazawa, Kohei Miyazono
Inhibitory Smads (I-Smads) have conserved carboxy-terminal MH2 domains but highly divergent amino-terminal regions when compared with receptor-regulated Smads (R-Smads) and common-partner Smads (co-Smads). Smad6 preferentially inhibits Smad signaling initiated by the bone morphogenetic protein (BMP) type I receptors ALK-3 and ALK-6, whereas Smad7 inhibits both transforming growth factor β (TGF-β)- and BMP-induced Smad signaling. I-Smads also regulate some non-Smad signaling pathways. Here, we discuss the vertebrate I-Smads, their roles as inhibitors of Smad activation and regulators of receptor stability, as scaffolds for non-Smad signaling, and their possible roles in the nucleus...
December 5, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27916280/novel-targeted-therapies-for-inflammatory-bowel-disease
#2
REVIEW
Mehmet Coskun, Severine Vermeire, Ole Haagen Nielsen
Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easily administered therapeutics that may be viable candidates for the management of IBD, such as antibodies against interleukin 6 (IL-6) and IL-12/23, small molecules including Janus kinase inhibitors, antisense oligonucleotide against SMAD7 mRNA, and inhibitors of leukocyte trafficking to intestinal sites of inflammation (e...
December 1, 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27892604/interleukin-il-6-modulates-transforming-growth-factor-%C3%AE-receptor-i-and-ii-tgf-%C3%AE-ri-and-ii-function-in-epidermal-keratinocytes
#3
Lerin R Luckett-Chastain, Mackenzie L Cottrell, Bethany M Kawar, Michael A Ihnat, Randle M Gallucci
It been shown that IL-6 modulates TGF-β1 expression in fibroblasts, however; what role IL-6 plays concerning TGF-βR expression and function in skin is unknown. Therefore, the aim of this study was to investigate the mechanism by which IL-6 might modulates TGF-β receptors in skin. Skin from WT, IL-6 overexpressing mice, and IL-6 treated keratinocyte cultures were analyzed for TGF-βRI and TGF-βRII expression via histology, PCR, and flow cytometry. Receptor function was assessed by cell migration, bromodeoxyuridine (BrdU) proliferation assays, and Smad7 expression and Smad2/3 phosphorylation...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27879343/strap-regulates-early-follicle-development-in-the-mouse-ovary
#4
Isam B Sharum, Sofia Granados-Aparici, Fiona C Warrander, Felicity P Tournant, Mark Fenwick
The molecular mechanisms involved in regulating the development of small, gonadotrophin-independent follicles are poorly understood; however, many studies have highlighted an essential role for TGFB ligands. Canonical TGFB signalling is dependent upon intracellular Smad proteins that regulate transcription. Strap has been identified in other tissues as an inhibitor of the TGFB-Smad signalling pathway. Therefore, in this study we aimed to determine the expression and role of Strap in the context of early follicle development...
November 22, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27878236/pyropia-yezoensis-peptide-promotes-collagen-synthesis-by-activating-the-tgf-%C3%AE-smad-signaling-pathway-in-the-human-dermal-fibroblast-cell-line-hs27
#5
Cho-Rong Kim, Young-Min Kim, Min-Kyeong Lee, In-Hye Kim, Youn-Hee Choi, Taek-Jeong Nam
Pyropia yezoensis (P. yezoensis) is a marine algae that exhibits antioxidant, anti-inflammatory, antitumor and anti-aging activities. In this study, we investigated the effects of the P. yezoensis peptide, PYP1‑5, on collagen synthesis in the human dermal fibroblast cell line Hs27. Skin aging is related to reduced collagen production and the activities of multiple enzymes, including matrix metalloproteinases (MMPs), which degrade collagen structure in the dermis, and tissue inhibitor of tissue inhibitor of metalloproteinases (TIMPs), which inhibit the action of MMPs...
November 18, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27876602/genistein-attenuates-d-galn-induced-liver-fibrosis-chronic-liver-damage-in-rats-by-blocking-the-tgf-%C3%AE-smad-signaling-pathways
#6
Ajaz Ahmad Ganai, Mohammad Husain
BACKGROUND AND AIM: Genistein is a major isoflavonoid abundantly found in soy. Earlier genistein has been reported to possess protective effect against a multitude of disorders including cancer. Previously we demonstrated the protective effects of Genistein in d-Galactosamine (D-GalN) induced fulminant hepatic failure (FHF) in rats. In present study, we evaluated the hepatoprotective activity of Genistein in rat model of chronic liver damage and liver fibrosis. METHODS: Liver fibrosis was induced by intraperitoneal injection of D-GalN (250 mg/kg BW) twice a week for 12 weeks...
November 19, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27876428/dmp-1-attenuates-oxidative-stress-and-inhibits-tgf-%C3%AE-activation-in-rats-with-diabetic-kidney-disease
#7
Na Du, Shunan Liu, Chongshuang Cui, Mo Zhang, Jibin Jia, Xia Cao
INTRODUCTION: DMP-1 supplement has a satisfactory effect on diabetic kidney disease in patients with whether T1DM or T2DM. Oxidative stress and TGF-β signal pathway activation are essential in the pathogenesis of DKD. We aim to investigate the effect of DMP-1 on oxidative stress and TGF-β activation in rats with DKD. MATERIALS AND METHODS: Male Wistar rats were enrolled and randomly allocated into five groups: Control group, STZ group (60 mg/kg, ip), DMP-1 low dose group (0...
November 23, 2016: Renal Failure
https://www.readbyqxmd.com/read/27872076/anti-schistosomiasis-liver-fibrosis-effects-of-chlorogenic-acid-through-il-13-mir-21-smad7-signaling-interactions-in-vivo-and-in-vitro
#8
Yao Wang, Fan Yang, Jun Xue, Xuan Zhou, Lei Luo, Qian Ma, Yun-Fei Chen, Juan Zhang, Shu-Ling Zhang, Lei Zhao
This study is to investigate the anti-Schistosomiasis liver fibrosis effects of chlorogenic acid (CGA) on IL-13/miR-21/Smad7 signaling interactions in hepatic stellate LX2 cell line and Schistosome-infected mice. The transfection was based on the GV273-miR-21-EGFP and GV369-miR-21-EGFP lentiviral system to up- or down-regulate miR-21 gene in LX2 cells. The mRNA expression of miR-21, Smad7 and connective tissue growth factor (CTGF) and protein expression of Smad7, CTGF, Smad1, p-Smad1, Smad2, p-Smad2, Smad2/3, p-Smad2/3, TGF-β receptor I and α-SMA were assayed...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27870967/osthole-inhibits-the-expressions-of-collagen-i-and-iii-through-smad-signaling-pathway-after-treatment-with-tgf-%C3%AE-1-in-mouse-cardiac-fibroblasts
#9
Jin-Cheng Liu, Feng Wang, Mei-Lin Xie, Zong-Qi Cheng, Qiong Qin, Lin Chen, Rong Chen
BACKGROUND: Osthole, a natural coumarin and bioactive compound isolated from the fruit of Cnidium monnieri (L.) Cusson, was reported to prevent isoprenaline-induced myocardial fibrosis in mice by inhibiting the transforming growth factor-β1 (TGF-β1) expression, but the underlying mechanism is still unclear. The aim of this study is to illuminate whether the mechanism of osthole inhibiting collagen I and III expressions is associated with Smad signaling pathway in mouse cardiac fibroblasts (CFs) treated with TGF-β1...
November 10, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27866193/mixed-aqueous-extract-of-salvia-miltiorrhiza-reduces-blood-pressure-through-inhibition-of-vascular-remodelling-and-oxidative-stress-in-spontaneously-hypertensive-rats
#10
Jing Zhang, Sheng Jun An, Jun Qiu Fu, Pei Liu, Tie Mei Shao, Manli Li, Xue Li, Zhan Jiao, Xi Qing Chai
BACKGROUND/AIMS: Salvia miltiorrhiza (SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), totally abbreviated as SABP. Although SM is often used to treat various cardiovascular diseases in traditional Chinese medicine, the efficacy and function of optimal compatibility ratio of SM's active ingredients (SABP) in the prevention and treatment of cardiovascular diseases remain uncertain...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27861825/high-smad7-sustains-inflammatory-cytokine-response-in-refractory-celiac-disease
#11
Silvia Sedda, Veronica De Simone, Irene Marafini, Gerolamo Bevivino, Roberta Izzo, Omero Alessandro Paoluzi, Alfredo Colantoni, Angela Ortenzi, Paolo Giuffrida, Gino R Corazza, Alessandro Vanoli, Antonio Di Sabatino, Francesco Pallone, Giovanni Monteleone
Refractory celiac disease (RCD) is a form of celiac disease (CD) resistant to gluten-free diet and associated with elevated risk of complications. Many effector cytokines over-produced in the gut of RCD patients are supposed to amplify the tissue-destructive immune response, but it remains unclear if the RCD-associated mucosal inflammation is sustained by defects in counter-regulatory mechanisms. The aim of the present study was to determine whether RCD-related inflammation is marked by high Smad7, an intracellular inhibitor of transforming growth factor (TGF)-β1 activity...
November 14, 2016: Immunology
https://www.readbyqxmd.com/read/27855406/scoparone-protects-against-pancreatic-fibrosis-via-tgf-%C3%AE-smad-signaling-in-rats
#12
Min Xu, Jing Cai, Hong Wei, Meng Zhou, Ping Xu, Hongmei Huang, Wanxin Peng, Fengyi Du, Aihua Gong, Youli Zhang
BACKGROUND/AIMS: This study was to investigate the influence of scoparone on pancreatic fibrosis in vitro and in vivo. METHODS: Pancreatic stellate cells (PSCs) were isolated from pancreas tissue blocks, and cultured for 3-5 generations for the experiment. PSCs were treated with scoparone in different doses as experimental groups, salvianolic acid B as a positive control and PBS as a blank group. We measured the effects of scoparone on cellular proliferation, oxidative stress, epithelial-mesenchymal transition (EMT), and pancreatic fibrosis...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27832357/emerging-biologics-in-inflammatory-bowel-disease
#13
REVIEW
Heyson Chi-Hey Chan, Siew Chien Ng
Early biologic therapy is recommended in patients with inflammatory bowel disease and poor prognostic factors and in those refractory to conventional medications. Anti-tumor necrosis factor (anti-TNF) agents are the most commonly used biologic agents. However, some patients may not have an initial response to anti-TNF therapy, and one-third will develop loss of response over time. Anti-TNF drugs can also be associated with side effects. In addition, the use of biologics is currently limited by their cost, especially in developing countries...
November 10, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27830743/fucose-containing-fraction-of-ling-zhi-enhances-lipid-rafts-dependent-ubiquitination-of-tgf%C3%AE-receptor-degradation-and-attenuates-breast-cancer-tumorigenesis
#14
Shu-Ming Tsao, Hsien-Yeh Hsu
Ganoderma lucidum exerts antitumor activity, but the mechanism of G. lucidum polysaccharides on cancer is unclear. Here, we demonstrated that a fucose-containing fraction of Ling-Zhi (FFLZ) reduced tumor size and suppressed metastasis in vivo. Furthermore, FFLZ inhibited breast cancer cell migration and altered the epithelial-to-mesenchymal transition (EMT) phenotype. Transforming growth factor-β receptor (TGFR) pathways act as key mediators to promote tumor progression and metastasis. We found that FFLZ down-regulated TGFR and downstream signaling pathways, including the phosphorylation of Smad2/3 and the expression of Smad4...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27797921/ccl20-is-negatively-regulated-by-tgf-%C3%AE-1-in-intestinal-epithelial-cells-and-reduced-in-crohn-s-disease-patients-with-a-successful-response-to-mongersen-a-smad7-antisense-oligonucleotide
#15
Irene Marafini, Ivan Monteleone, Vincenzo Dinallo, Davide Di Fusco, Veronica De Simone, Federica Laudisi, Massimo Claudio Fantini, Antonio Di Sabatino, Francesco Pallone, Giovanni Monteleone
BACKGROUND AND AIM: The chemokine CCL20 is over-produced in epithelium of Crohn's disease [CD] patients and contributes to recruiting immune cells to inflamed gut. Tumour necrosis factor-α [TNF-α] is a powerful inducer of CCL20 in intestinal epithelial cells. In CD, high levels of Smad7 block the activity of transforming growth factor-β1 [TGF-β1], a negative regulator of TNF signalling. We investigated whether intestinal epithelial cell-derived CCL20 is negatively regulated by TGF-β1 and whether Smad7 knock-down reduces CCL20 in CD...
October 25, 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/27794120/bmp-smad-id-promotes-reprogramming-to-pluripotency-by-inhibiting-p16-ink4a-dependent-senescence
#16
Yohei Hayashi, Edward C Hsiao, Salma Sami, Mariselle Lancero, Christopher R Schlieve, Trieu Nguyen, Koyori Yano, Ayako Nagahashi, Makoto Ikeya, Yoshihisa Matsumoto, Ken Nishimura, Aya Fukuda, Koji Hisatake, Kiichiro Tomoda, Isao Asaka, Junya Toguchida, Bruce R Conklin, Shinya Yamanaka
Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling. Contrary to a previous study, here we show that FOP fibroblasts showed an increased efficiency of induced pluripotent stem cell (iPSC) generation. This positive effect was attenuated by inhibitors of BMP-SMAD signaling (Dorsomorphin or LDN1931890) or transducing inhibitory SMADs (SMAD6 or SMAD7). In normal fibroblasts, the efficiency of iPSC generation was enhanced by transducing mutant ACVR1 (617G > A) or SMAD1 or adding BMP4 protein at early times during the reprogramming...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27780942/-role-of-inhibitory-transforming-growth-factor-%C3%AE-signal-smad7-in-helicobacter-pylori-associated-gastric-damage
#17
Ho Jae Lee, Jong Min Park, Ki Baik Hahm
Background/Aims: Transforming growth factor-beta (TGF-β) is a cytokine implicated in the susceptibility, development, and progression of gastrointestinal cancer and certain other neoplasms. In the later stages of cancer, TGF-β not only acts as a bystander of host-immune response, but also contributes to cell growth, invasion, and metastasis. In the current study, we generated gastric mucosal cells that stably express Smad7, and explored the Helicobacter pylori-associated biological changes between mock-transfected and Smad7-transfected RGM1 cells...
October 25, 2016: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/27747000/suberoylanilide-hydroxamic-acid-attenuates-paraquat-induced-pulmonary-fibrosis-by-preventing-smad7-from-deacetylation-in-rats
#18
Shan-Shan Rao, Xiang-Yan Zhang, Ming-Jun Shi, Ying Xiao, Ying-Ying Zhang, Yuan-Yuan Wang, Chang-Zhi Zhang, Song-Jun Shao, Xin-Mei Liu, Bing Guo
BACKGROUND: Recent evidence suggests that a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has anti-fibrotic effect. However, the exact mechanism of its anti-fibrotic potential remains is unclear. In this study, we investigated the molecular mechanism of SAHA in attenuating pulmonary fibrosis by regulating stability of Smad7 in paraquat (PQ)-induced lung fibrosis animal model and cultured pulmonary fibroblasts. METHODS: Rats with paraquat-induced lung fibrosis were fed with a SAHA solution (15 mg/kg) by gastric gavage...
September 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27742678/mir-181a-5p-regulates-3t3-l1-cell-adipogenesis-by-targeting-smad7-and-tcf7l2
#19
Dan Ouyang, Lifeng Xu, Lihua Zhang, Dongguang Guo, Xiaotong Tan, Xiaofang Yu, Junjie Qi, Yaqiong Ye, Qihong Liu, Yongjiang Ma, Yugu Li
MicroRNAs are highly conserved non-coding small RNAs participating in almost all kinds of biological activities. MiR-181a has been reported to be involved in the differentiation of porcine primary preadipocytes, but the profound effect of miR-181a-5p on 3T3-L1 adipocyte differentiation and proliferation is still unclear. In this study, we found that supplementation of miR-181a-5p in 3T3-L1 cells significantly promoted the adipogenesis and inhibited cell proliferation with increased expression of adipogenic marker genes including peroxisome proliferator-activated receptor gamma (Pparγ), CCAAT/enhancer-binding protein alpha (C/ebpα), fatty acid-binding protein 4 (Fabp4), and Adiponectin, accompanied by an accumulation of lipid droplet, an increase of triglyceride content, and a decrease of cell proliferation...
October 14, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27731365/intraarticular-overexpression-of-smad7-ameliorates-experimental-arthritis
#20
Shih-Yao Chen, Ai-Li Shiau, Chao-Liang Wu, Chrong-Reen Wang
Rheumatoid arthritis (RA) and Crohn's disease (CD) are autoimmune disorders with a crosstalk between their pathogenesis such as increased expression of TNF in the target organs. Despite a successful clinical trial with an oral Smad7 antisense oligonucleotide in CD, intraarticular (i.a.) modulation of Smad7 expression has not been performed in rheumatoid joint yet. In this study, contradictory to the findings in CD mucosa, higher levels of pSmad2/3 were found in RA synovium. In vitro experiments with synovial fibroblasts revealed that higher acetylated Smad7 expression was associated with lower activation status...
October 12, 2016: Scientific Reports
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