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https://www.readbyqxmd.com/read/28108300/transforming-growth-factor-beta-inducible-early-gene-1-tieg1-represses-smad7-mediated-activation-of-tgf-%C3%AE-1-smad-signaling-in-keloid-pathogenesis
#1
Zhi-Cheng Hu, Fen Shi, Peng Liu, Jian Zhang, Dong Guo, Xiao-Ling Cao, Chu-Fen Chen, Shanqiang Qu, Jia-Yuan Zhu, Bing Tang
Transforming growth factor β (TGF-β)/Smad signaling plays a key role in excessive fibrosis and keloid formations. Smad7 is a negative feedback regulator that prevents activation of TGF-β/Smad signaling. However, the regulatory mechanism for Smad7 in the keloid pathogenic process remains elusive. Here, we show that expression of TGF-β inducible early gene-1 (TIEG1) is markedly higher in keloid fibroblasts (KFs), while protein, mRNA, and promoter activity levels of Smad7 are decreased. When TIEG1 was knocked down with small interfering RNA (siRNA), both the promoter activity and protein expression of Smad7 were increased, while collagen production and the proliferation, migration, and invasion of KFs were decreased...
January 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28107197/mtdh-promotes-glioma-invasion-through-regulating-mir-130b-cernas
#2
Liping Tong, Ming Chu, Bingqing Yan, Weiyi Zhao, Shuang Liu, Wei Wei, Huihuang Lou, Shengkun Zhang, Shuai Ma, Juan Xu, Lanlan Wei
Cell invasion is crucial for high mortality and recurrence rate in glioma. Epithelial-mesenchymal transition (EMT) is an important step in cancer invasion. Metadherin (MTDH) contributes to EMT in several cancers, but the role and mechanism of MTDH in EMT-like process of glioma remain unknown. Here we demonstrate that MTDH was overexpressed in glioma tissues and cells and induced EMT-like change and invasion of glioma cells. Interestingly, MTDH could modulate the expression of a group of glioma-related miRNAs...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28096433/sex-differences-in-the-development-of-prolactinoma-in-mice-overexpressing-hcg%C3%AE-role-of-tgf%C3%AE-1
#3
Erika Yanil Faraoni, María Andrea Camilletti, Alejandra Inés Abeledo Machado, Laura Daniela Ratner, Fernanda De Fino, Ilpo T Huhtaniemi, Susana B Rulli, Graciela Diaz-Torga
Female transgenic mice that overexpress the human chorionic gonadotrophin β subunit (hCGβ+) develop prolactinomas, while hCGβ+ males do not. The high levels of circulating hCG induces massive luteinization in the ovary of hCGβ+ females, and progesterone becomes the primary steroid hormone produced, but estradiol remains at physiological level. The involvement of high levels of progesterone in lactotroph proliferation is not clearly understood; hence the pathogenesis of prolactinomas in hCGβ+ females remains unclear...
January 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28095858/mir-4775-promotes-colorectal-cancer-invasion-and-metastasis-via-the-smad7-tgf%C3%AE-mediated-epithelial-to-mesenchymal-transition
#4
Senlin Zhao, Hongcheng Sun, Weiliang Jiang, Yushuai Mi, Dongyuan Zhang, Yugang Wen, Dantong Cheng, Huamei Tang, Shaohan Wu, Yang Yu, Xisheng Liu, Weiyingqi Cui, Meng Zhang, Xiaofeng Sun, Zongguang Zhou, Zhihai Peng, Dongwang Yan
BACKGROUND: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression...
January 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28070019/smad7-polymorphisms-and-colorectal-cancer-risk-a-meta-analysis-of-case-control-studies
#5
Yongsheng Huang, Wenting Wu, Meng Nie, Chuang Li, Lin Wang
Mothers against decapentaplegic homolog 7 (SMAD7) inhibits the transforming growth factor-β (TGF-β) signaling pathway, which regulates carcinogenesis and cancer progression. A number of studies have reported that SMAD7 polymorphisms (rs4464148, rs4939827, and rs12953717) are associated with colorectal cancer (CRC) risk, but the results from these studies remain conflicting. To determine a more precise estimation of the relationship between SMAD7 and CRC, we undertook a large-scale meta-analysis of 63 studies, which included a total of 187,181 subjects (86,585 cases and 100,596 controls)...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/28061442/genetic-variants-in-the-tgf%C3%AE-signaling-pathway-influence-expression-of-mirnas-in-colon-and-rectal-normal-mucosa-and-tumor-tissue
#6
Martha L Slattery, Andromahi Trivellas, Andrew J Pellatt, Lila E Mullany, John R Stevens, Roger K Wolff, Jennifer S Herrick
The TGF-β signaling pathway is involved in regulation of cell growth, angiogenesis, and metastasis. We test the hypothesis that genetic variation in the TGF-β signaling pathway alters miRNA expression.We use data from 1188 colorectal cancer cases to evaluate associations between 80 SNPs in 21 genes.Seven variants eIF4E rs12498533, NFκB1 rs230510, TGFB1 rs4803455, TGFBR1 rs1571590 and rs6478974, SMAD3 rs3743343, and RUNX1 rs8134179 were associated with expression level of miRNAs in normal colorectal mucosa...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057752/foxo1-inhibits-accelerated-%C3%AE-cell-aging-in-pancreas-specific-smad7-mutant-mice
#7
Xiangwei Xiao, Congde Chen, Ping Guo, Ting Zhang, Shane Fischbach, Joseph Carl Fusco, Chiyo Shiota, Krishna Prasadan, H Henry Dong, George K Gittes
The mechanisms underlying the effects of exocrine dysfunction on the development of diabetes remain largely unknown. Here, we show that pancreatic depletion of SMAD7 resulted in age-dependent increases in β-cell dysfunction, with accelerated glucose intolerance, followed by overt diabetes. The accelerated β-cell dysfunction and loss of proliferation capacity, two features of β-cell aging, appeared to be non-cell-autonomous, secondary to the adjacent exocrine failure as a bystander effect. Increased FoxO1 acetylation and nuclear retention was followed by progressive FoxO1 loss in β-cells, which marked the onset of diabetes...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28054334/comprehensive-candidate-gene-analysis-for-symptomatic-or-asymptomatic-outcomes-of-leishmania-infantum-infection-in-brazil
#8
Jason L Weirather, Priya Duggal, Eliana L Nascimento, Gloria R Monteiro, Daniella R Martins, Henio G Lacerda, Michaela Fakiola, Jenefer M Blackwell, Selma M B Jeronimo, Mary E Wilson
Genetic risk factors contribute to asymptomatic versus symptomatic visceral leishmaniasis (VL) outcomes following infection with Leishmania infantum. We therefore carried out a family-based (n = 918 post-quality control fully genotyped and phenotyped individuals) candidate gene study for symptomatic VL or asymptomatic delayed-type hypersensitivity (DTH) skin test phenotypes in highly endemic neighborhoods of northeast Brazil. A total of 248 SNPs were genotyped in 42 genes selected as candidates on the basis of prior genetic, immunological, and transcriptional profiling studies...
January 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/28013146/rational-design-of-cyclic-peptides-to-disrupt-tgf-%C3%AE-smad7-signaling-in-heterotopic-ossification
#9
Biao Zhong, Chi Zhang, Shang Guo, Changqing Zhang
The human TGF-β/SMAD7 signaling has been recognized as an attractive target of heterotopic ossification (HO). Here, we report a successful rational design of cyclic peptides to disrupt the signaling pathway by targeting TGF-β-receptor complex. The intermolecular interaction between TGF-β and its cognate receptor is characterized in detail using molecular dynamics simulation, binding energetic analysis, and alanine scanning. With the computational analysis a binding loop of receptor protein is identified that plays an essential role in the peptide-mediated TGF-β-receptor interaction...
December 7, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28009003/acetyl-11-keto-%C3%AE-boswellic-acid-attenuates-prooxidant-and-profibrotic-mechanisms-involving-transforming-growth-factor-%C3%AE-1-and-improves-vascular-remodeling-in-spontaneously-hypertensive-rats
#10
Peijin Shang, Wenxing Liu, Tianlong Liu, Yikai Zhang, Fei Mu, Zhihui Zhu, Lingfei Liang, Xiaohu Zhai, Yi Ding, Yuwen Li, Aidong Wen
Vascular remodeling is an important complication of hypertension with oxidative stress-related profibrotic pathways involved. The transforming growth factor β1 (TGF-β1) has been shown to be a potential target of vasoprotection, and has multiple roles in vascular remodeling. Acetyl-11-Keto-β-Boswellic Acid (AKBA) is one of the active principles of Boswellic acids, and shows antioxidant activity in many diseases. The study is to determine effects of AKBA on systemic oxidative stress of hypertension and vascular remodeling...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28003811/identification-and-characterization-of-a-novel-association-between-dietary-potassium-and-risk-of-crohn-s-disease-and-ulcerative-colitis
#11
Hamed Khalili, Sakshi Malik, Ashwin N Ananthakrishnan, John J Garber, Leslie M Higuchi, Amit Joshi, Joanna Peloquin, James M Richter, Kathleen O Stewart, Gary C Curhan, Amit Awasthi, Vijay Yajnik, Andrew T Chan
BACKGROUND: Recent animal studies have identified that dietary salt intake may modify the risk and progression of autoimmune disorders through modulation of the IL-23/TH17 pathway, which is critical in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We conducted a prospective study of U.S. women enrolled in the Nurses' Health Study (NHS) and NHSII who provided detailed and validated information on diet and lifestyle beginning in 1984 in NHS and 1991 in NHSII...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27996082/activin-smad-signaling-is-required-for-maintenance-of-porcine-ips-cell-self-renewal-through-upregulation-of-nanog-and-oct4-expression
#12
Fan Yang, Ning Wang, Yaxian Wang, Tong Yu, Huayan Wang
Porcine induced pluripotent stem cells (piPSCs) retain the enormous potential for farm animal reproduction and translational medicine, and have been reported by many laboratories worldwide. Some piPSC lines were bFGF-dependence and showed mouse EpiSC-like morphology; other lines were LIF-dependence and showed mouse ESC-like morphology. Metastable state of piPSC line that required both LIF and bFGF was also reported. Because bona fide pig embryonic stem cells were not available, uncovering piPSC state-specific regulatory circuitries was the most important task...
December 20, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27996004/microrna-182-targets-smad7-to-potentiate-tgf%C3%AE-induced-epithelial-mesenchymal-transition-and-metastasis-of-cancer-cells
#13
Jingyi Yu, Rong Lei, Xueqian Zhuang, Xiaoxun Li, Gang Li, Sima Lev, Miguel F Segura, Xue Zhang, Guohong Hu
The transforming growth factor β (TGFβ) pathway plays critical roles during cancer cell epithelial-mesenchymal transition (EMT) and metastasis. SMAD7 is both a transcriptional target and a negative regulator of TGFβ signalling, thus mediating a negative feedback loop that may potentially restrain TGFβ responses of cancer cells. Here, however, we show that TGFβ treatment induces SMAD7 transcription but not its protein level in a panel of cancer cells. Mechanistic studies reveal that TGFβ activates the expression of microRNA-182 (miR-182), which suppresses SMAD7 protein...
December 20, 2016: Nature Communications
https://www.readbyqxmd.com/read/27991776/capsaicin-inhibits-dimethylnitrosamine-induced-hepatic-fibrosis-by-inhibiting-the-tgf-%C3%AE-1-smad-pathway-via-peroxisome-proliferator-activated-receptor-gamma-activation
#14
Jae Ho Choi, Sun Woo Jin, Chul Yung Choi, Hyung Gyun Kim, Gi Ho Lee, Yong An Kim, Young Chul Chung, Hye Gwang Jeong
Capsaicin (CPS) exerts many pharmacological effects, but any possible influence on liver fibrosis remains unclear. Therefore, we evaluated the inhibitory effects of CPS on dimethylnitrosamine (DMN) and TGF-β1-induced liver fibrosis in rats and hepatic stellate cells (HSCs). CPS inhibited DMN-induced hepatotoxicity, NF-κB activation, and collagen accumulation. CPS also suppressed the DMN-induced increases in α-SMA, collagen type I, MMP-2, and TNF-α. In addition, CPS inhibited DMN-induced TGF-β1 expression (from 2...
January 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27990439/effect-of-exogenous-fetuin-a-on-tgf-%C3%AE-smad-signaling-in-hepatic-stellate-cells
#15
Yulai Zhou, Shuang Yang, Pan Zhang
Objective. To explore the effects of low concentration of exogenous fetuin-A intervention on TGF-β1 induced LX2 cells through detection of the expression of mRNA and protein of Smad2, Smad3, and Smad7. Methods. MTT assay was used to detect the LX2 cells proliferation and the regression equation calculating software was applied to determine IC50 of fetuin-A. RT-PCR was used to determine the relative content of Smad2, Smad3, and Smad7 mRNA in LX2 cells. Western blot was used to detect the LX2 cells relative content of Smad2, Smad3, Smad7 protein expression, respectively...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27974675/nedd9-may-regulate-hepatocellular-carcinoma-cell-metastasis-by-promoting-epithelial-mesenchymal-transition-and-stemness-via-repressing-smad7
#16
Zhipeng Wang, Min Shen, Peng Lu, Xiao Li, Shaojun Zhu, Shuqiang Yue
Overexpression of neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is a prognostic marker of many cancers, including hepatocellular carcinoma (HCC). However, the functions and mechanisms of NEDD9 are unclear. We found that upregulation of NEDD9 promoted migration, invasion and cell-to-extracellular matrix adhesion of HCC cells. NEDD9 also induced the epithelial-mesenchymal transition (EMT) and expression of matrix metalloprotein 2 (MMP2). Increased aldehyde dehydrogenase (ALDH) activity and CD133-positive cells were observed in HCC cells with high expression of NEDD9, corresponding to greater sphere formation in cancer stem cells (CSCs)...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27967316/adipogenic-impairment-of-adipose-tissue-derived-mesenchymal-stem-cells-in-subjects-with-metabolic-syndrome-possible-protective-role-of-fgf2
#17
Wilfredo Oliva-Olivera, Leticia Coín-Aragüez, Said Lhamyani, Mercedes Clemente-Postigo, Juan Alcaide Torres, Maria Rosa Bernal-López, Rajaa El Bekay, Francisco José Tinahones
CONTEXT: The decreased expansion capacity of adipose tissue plays a crucial role in the onset of disorders associated with metabolic syndrome. Objetive: The aim of this study was to examine the state of adipose tissue-derived mesenchymal stem cells (ASCs) from obese subjects with different metabolic profiles. DESIGN: This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. SETTING: University Hospital Patients and Intervention: Patients who underwent either bariatric surgery (20 morbidly obese) or cholecystectomy (40 subjects) participated in the study...
December 14, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27942027/correction-elevating-clic4-in-multiple-cell-types-reveals-a-tgf-%C3%AE-dependent-induction-of-a-dominant-negative-smad7-splice-variant
#18
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0161410.].
2016: PloS One
https://www.readbyqxmd.com/read/27920040/regulation-of-tgf-%C3%AE-family-signaling-by-inhibitory-smads
#19
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
#20
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
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