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https://www.readbyqxmd.com/read/28220374/lipopolysaccharide-activates-toll-like-receptor-4-and-prevents-cardiac-fibroblast-to-myofibroblast-differentiation
#1
Samir Bolívar, Roxana Santana, Pedro Ayala, Rodolfo Landaeta, Pía Boza, Claudio Humeres, Raúl Vivar, Claudia Muñoz, Viviana Pardo, Samuel Fernandez, Renatto Anfossi, Guillermo Diaz-Araya
Bacterial lipopolysaccharide (LPS) is a known ligand of Toll-like receptor 4 (TLR4) which is expressed in cardiac fibroblasts (CF). Differentiation of CF to cardiac myofibroblasts (CMF) is induced by transforming growth factor-β1 (TGF-β1), increasing alpha-smooth muscle actin (α-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-β1 signaling was described; however, it has not been studied whether in CF and CMF the expression of α-SMA induced by TGF-β1 is antagonized by LPS and the mechanism involved...
February 20, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28218435/a-low-frequency-variant-in-smad7-modulates-tgf-%C3%AE-signaling-and-confers-risk-for-colorectal-cancer-in-chinese-population
#2
Jiaoyuan Li, Li Zou, Ying Zhou, Lu Li, Ying Zhu, Yang Yang, Yajie Gong, Jiao Lou, Juntao Ke, Yi Zhang, Jianbo Tian, Danyi Zou, Xiating Peng, Jiang Chang, Jing Gong, Rong Zhong, Xiaobo Zhou, Xiaoping Miao
The TGF-β pathway plays an essential role in regulating cell proliferation and differentiation. GWASs and candidate approaches have identified a battery of genetic variants in the TGF-β pathway contributing to colorectal cancer (CRC). However, most of the significant variants are common variants and their functions remain ambiguous. To identify causal variants with low-frequency in the TGF-β pathway contributing to CRC susceptibility in Chinese population, we performed targeted sequencing of 12 key genes in TGF-β signaling in CRC patients followed by a two-stage case-control study with a total of 5109 cases and 5169 controls...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28208683/plasma-gelsolin-induced-glomerular-fibrosis-via-the-tgf-%C3%AE-1-smads-signal-transduction-pathway-in-iga-nephropathy
#3
Lei Zhang, Changsong Han, Fei Ye, Yan He, Yinji Jin, Tianzhen Wang, Yiqi Wu, Yang Jiang, Fengmin Zhang, Xiaoming Jin
Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway...
February 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207735/long-non-coding-rna-hotair-inhibits-mir-17-5p-to-regulate-osteogenic-differentiation-and-proliferation-in-non-traumatic-osteonecrosis-of-femoral-head
#4
Biaofang Wei, Wei Wei, Baoxiang Zhao, Xiaxia Guo, Song Liu
BACKGROUND AND AIM: The biological functions of non-coding RNAs (ncRNAs) have been widely identified in many human diseases. In the present study, the relationship between long non-coding RNA HOTAIR and microRNA-17-5p (miR-17-5p) and their roles in osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head (ONFH) were investigated. METHODS: The expression levels of HOTAIR and miR-17-5p in the mesenchymal stem cells (MSCs) derived from patients with non-traumatic ONFH and osteoarthritis (OA) were examined by real-time PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28192402/loss-of-klf4-and-consequential-downregulation-of-smad7-exacerbate-oncogenic-tgf-%C3%AE-signaling-in-and-promote-progression-of-hepatocellular-carcinoma
#5
H Sun, Z Peng, H Tang, D Xie, Z Jia, L Zhong, S Zhao, Z Ma, Y Gao, L Zeng, R Luo, K Xie
Hyperactivation of transforming growth factor-β (TGF-β) signaling pathway is a common feature of hepatocellular carcinoma (HCC) progression. However, the driver factors leading to enhanced TGF-β activity are not well characterized. Here, we explore the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic TGF-β signaling in human HCC. The expression of KLF4 and TGF-β signaling components in primary HCC and their clinicopathologic relevance and significance was evaluated by using tissue microarray and immunohistochemistry...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192117/nr2f2-inhibits-smad7-expression-and-promotes-tgf-%C3%AE-dependent-epithelial-mesenchymal-transition-of-crc-via-transactivation-of-mir-21
#6
Hao Wang, Lei Nie, Lei Wu, Qiufang Liu, Xueyan Guo
Metastasis is one of the most decisive factors influencing CRC patient prognosis and current studies suggest that a molecular mechanism known as EMT broadly regulates cancer metastasis. NR2F2 is a key molecule in the development of CRC, but the roles and underlying mechanisms of NR2F2 in TGF-β induced EMT in CRC remain largely unknown. In the current study, we were interested to examine the role of NR2F2 in the TGF-β-induced EMT in CRC. Here, we found NR2F2 was upregulated in CRC cells and promotes TGF-β-induced EMT in CRC...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28167776/tgf-%C3%AE-inhibitor-smad7-regulates-dendritic-cell-induced-autoimmunity
#7
Dominika Lukas, Nir Yogev, Junda M Kel, Tommy Regen, Ilgiz A Mufazalov, Yilang Tang, Florian Wanke, Boris Reizis, Werner Müller, Florian C Kurschus, Marco Prinz, Ingo Kleiter, Björn E Clausen, Ari Waisman
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28163383/mitigated-nsaid-induced-apoptotic-and-autophagic-cell-death-with-smad7-overexpression
#8
Ho-Jae Lee, Jong Min Park, Ki Baik Hahm
Non-steroidal anti-inflammatory drugs damaged gastrointestinal mucosa in cyclooxygenase-dependent and -independent pathway, among which apopototic or autophagic cell death in gastrointestinal cells might be one of key cytotoxic mechanisms responsible for NSAID-induced damages. Therefore, alleviating this cell death after NSAIDs can be a rescuing strategy. In this study, we explored the role of Smad7 on NSAID-induced cytotoxicity in gastric epithelial cells. Using RGM1 cells, we have compared biological changes between mock-transfected and Smad7-overexpressed cells...
January 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28144028/current-and-emerging-therapeutic-targets-for-ibd
#9
REVIEW
Markus F Neurath
Various therapeutic advances have led to a paradigm shift in the clinical management of patients with IBD. The introduction of immunosuppressive (such as azathioprine) and biologic agents (such as TNF blockers) has markedly reduced the need to use corticosteroids for therapy. Furthermore, the α4β7 integrin blocker vedolizumab has been introduced for clinical IBD therapy. Moreover, various new inhibitors of cytokines (for example, IL-6-IL-6R and IL-12-IL-23 blockers or apremilast), modulators of cytokine signalling events (for example, JAK inhibitors or SMAD7 blocker), inhibitors of transcription factors (for example, GATA3 or RORγt) and new anti-adhesion and anti-T-cell-activation and migration strategies (for example, β7 integrin, sphingosine 1-phosphate receptors and MAdCAM1 inhibitors, regulatory T-cell therapy and stem cells) are currently being evaluated in controlled clinical trials...
February 1, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28142299/tgf-%C3%AE-1-protects-intestinal-integrity-and-influences-smads-and-mapk-signal-pathways-in-ipec-j2-after-tnf-%C3%AE-challenge
#10
Kan Xiao, Shuting Cao, Lefei Jiao, Zehe Song, Jianjun Lu, Caihong Hu
The aim of this study was to investigate the protective effects of TGF-β1 on intestinal epithelial barrier, as well as canonical Smad and MAPK signal pathways involved in these protection processes by a IPEC-J2 model stimulated with TNF-α. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of TGF-β1. The results showed that TGF-β1 pretreatment ameliorated TNF-α-induced intestinal epithelial barrier disturbances as indicated by decrease of transepithelial electrical resistance (TER) and increase of paracellular permeability...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28134936/hepatocyte-specific-smad7-deletion-accelerates-den-induced-hcc-via-activation-of-stat3-signaling-in-mice
#11
T Feng, J Dzieran, X Yuan, A Dropmann, T Maass, A Teufel, S Marhenke, T Gaiser, F Rückert, I Kleiter, S Kanzler, M P Ebert, A Vogel, P Ten Dijke, S Dooley, N M Meindl-Beinker
TGF-β signaling in liver cells has variant roles in the dynamics of liver diseases, including hepatocellular carcinoma (HCC). We previously found a correlation of high levels of the important endogenous negative TGF-β signaling regulator SMAD7 with better clinical outcome in HCC patients. However, the underlying tumor-suppressive molecular mechanisms are still unclear. Here, we show that conditional (TTR-Cre) hepatocyte-specific SMAD7 knockout (KO) mice develop more tumors than wild-type and corresponding SMAD7 transgenic mice 9 months after diethylnitrosamine (DEN) challenge, verifying SMAD7 as a tumor suppressor in HCC...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28123501/identification-of-the-molecular-mechanisms-underlying-dilated-cardiomyopathy-via-bioinformatic-analysis-of-gene-expression-profiles
#12
Hu Zhang, Zhuo Yu, Jianchao He, Baotong Hua, Guiming Zhang
In the present study, gene expression profiles of patients with dilated cardiomyopathy (DCM) were re-analyzed with bioinformatics tools to investigate the molecular mechanisms underlying DCM. Gene expression dataset GSE3585 was downloaded from Gene Expression Omnibus, which included seven heart biopsy samples obtained from patients with DCM and five healthy controls. Differential analysis was performed using a Limma package in R to screen for differentially expressed genes (DEGs). Functional enrichment analysis was subsequently conducted for DEGs using the Database for Annotation, Visualization and Integration Discovery...
January 2017: Experimental and Therapeutic Medicine
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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