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Smad7 AND TGF beta

Ganping Bai, Guohe Yan, Guojian Wang, Ping Wan, Ronghua Zhang
Hepatic fibrosis (HF), a wound-healing response to a variety of chronic stimuli, is characterized by the excessive synthesis of extracellular matrix (ECM) proteins by hepatic stellate cells (HSC) and eventually the development of hepatic cirrhosis. Turtle shell pill (TSP) is a common traditional Chinese medicine used for preventing and treating HF and early hepatic cirrhosis, but its side-effects and the shortage of ingredients limit its clinical application. In addition, its mechanism of action is not clear...
September 9, 2016: Oncology Reports
Anjali Shukla, Yihan Yang, Sara Madanikia, Yan Ho, Mangmang Li, Vanesa Sanchez, Christophe Cataisson, Jing Huang, Stuart H Yuspa
CLIC4 (Chloride intracellular channel 4) belongs to a family of putative intracellular chloride channel proteins expressed ubiquitously in multiple tissues. CLIC4 is predominantly soluble and traffics between the cytoplasm and nucleus and participates in cell cycle control and differentiation. Transforming growth factor beta (TGF-β) elevates CLIC4, which enhances TGF-β signaling through CLIC4 mediated stabilization of phospho-Smad2/3. CLIC4 is essential for TGF-β induced conversion of fibroblasts to myofibroblasts and expression of matrix proteins, signaling via the p38MAPK pathway...
2016: PloS One
Gabriel Gallo-Oller, Arabel Vollmann-Zwerenz, Bárbara Meléndez, Juan A Rey, Peter Hau, Javier Dotor, Javier S Castresana
Glioblastoma (GBM) is the most prevalent malignant primary brain tumor, accounting for 60-70% of all gliomas. Current median patient survival time is 14-16 months after diagnosis. Numerous efforts in therapy have not significantly altered the nearly uniform lethality of this malignancy. The Transforming Growth Factor beta (TGF-β) signaling pathway plays a key role in GBM and is implicated in proliferation, invasion and therapy resistance. Several inhibitors of the TGF-β pathway have entered clinical trials or are under development...
October 10, 2016: Cancer Letters
Chaoju Hua, Zishuai Wang, Jianbing Zhang, Xing Peng, Xinhua Hou, Yalan Yang, Kui Li, Zhonglin Tang
SMAD7 promotes and enhances skeletal muscle differentiation by inhibiting transforming growth factor beta (TGF-β)/activin signaling and bone morphogenetic protein (BMP) pathways. However, its function, the mechanism regulating its translation, and its association with production meat traits remain unclear in pigs. In this study, we explored SMAD7 gene spatio-temporal and tissue distribution, conducted a single nucleotide polymorphism association analysis, and examined regulation of its expression during skeletal muscle development...
April 2016: Molecular Biology Reports
Krishnan MohanKumar, Kopperuncholan Namachivayam, Kalyan C Chapalamadugu, Steven A Garzon, Muralidhar H Premkumar, Srinivas M Tipparaju, Akhil Maheshwari
BACKGROUND: Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. Based on our recent findings of increased Smad7 expression in surgically resected bowel affected by NEC, we hypothesized that NEC macrophages undergo inflammatory activation because increased Smad7 expression renders these cells resistant to normal, gut-specific, transforming growth factor (TGF)-β-mediated suppression of inflammatory pathways. METHODS: We used surgically resected human NEC tissue, murine models of NEC-like injury, bone marrow-derived and intestinal macrophages, and RAW264...
June 2016: Pediatric Research
Amal Ahmed Abd El-Fattah, Nermin Abdel Hamid Sadik, Olfat Gamil Shaker, Amal Mohamed Kamal
A wide variety of genes have been associated with colorectal cancer (CRC) development and progression. The SMAD7 gene encodes an intracellular protein, which inhibits the transforming growth factor beta (TGF-β) signaling pathway, thereby having a key role in the control of neoplastic processes in various organs. The CHI3L1 gene encodes glycoprotein YKL-40, which plays a role in cell proliferation, anti-apoptosis, and angiogenesis. The present study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) SMAD7 rs4939827 and CHI3L1 rs4950928, as well as circulating TGFβ-1 and YKL-40 levels with CRC in an Egyptian population of 77 CRC patients and 36 healthy controls...
July 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xiaomei Wang, Changzheng Mu, Tianchi Mu, Lili Gao, Yaxue Zhao, Yangyi Zhang, Zhimian Zhang
BACKGROUND: The aim of this study was to explore the effect of Tongxinluo on myocardial fibrosis in diabetic rats and its possible mechanism of action. METHODS: Diabetic rat models were established and then divided into three groups: control, diabetes, and Tongxinluo groups. Heart function and myocardial interstitial collagen volume fraction were investigated, and the protein and mRNA expression levels of transforming growth factor beta 1 (TGF-β1), Smad3, and Smad7 were measured...
March 2016: Journal of the Chinese Medical Association: JCMA
Fu-rong Wu, Ling Jiang, Xiao-li He, Peng-li Zhu, Jun Li
Liver fibrosis is a common pathological process for chronic liver injury caused by multiple etiological factors and an inevitable phase leading to liver cirrhosis. According to the previous studies, hesperidin (HDN) shows a very good protective effect on CCl4-induced chemical hepatic fibrosis in rats. In this experiment, based on the findings of the previous studies, a platelet-derived growth factor (PDGF)-induced HSC-T6 model was established to observe the inhibitory effect of HDN on HSC-T6 proliferation. The ELISA method was adopted to detect the content of collagen I in HSC-T6 supernatant...
July 2015: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Jingying Hou, Ping Yan, Tianzhu Guo, Yue Xing, Shaoxin Zheng, Changqing Zhou, Hui Huang, Huibao Long, Tingting Zhong, Quanhua Wu, Jingfeng Wang, Tong Wang
BACKGROUND: In this study, we hypothesized that CSCs mediated the expression of Cx43 after transplantation post MI via the ANG II/AT1R/TGF-beta1 signaling pathway. METHODS: Myocardial infarction (MI) was induced in twenty male Sprague-Dawley rats. The rats were randomized into two groups and were then received the injection of 5 × 10(6) CSCs labeled with PKH26 in phosphate buffer solution (PBS) or equal PBS alone into the infarct anterior ventricular free wall two weeks after MI...
December 2015: Experimental and Molecular Pathology
Yanhua Zhang, Songyan Wang, Shengmao Liu, Chunguang Li, Ji Wang
Smads are the key intermediates of canonical transforming growth factor-beta (TGF-β) signaling. These intermediates are divided into three distinct subgroups based on their role in TGF-β family signal transduction: Receptor-regulated Smads (R-Smads) 1, 2, 3, 5 and 8, common Smad4, and inhibitory Smads6 and 7. TGF-β signaling through Smad pathway involves phosphorylation, ubiquitination, sumoylation, acetylation, and protein-protein interactions with mitogen-activated protein kinases, PI3K-Akt/PKB, and Wnt/GSK-3...
December 2015: International Urology and Nephrology
Sihui Li, Qian Fan, Shaolin He, Tingting Tang, Yuhua Liao, Jiangjiao Xie
BACKGROUND: CD4+CD25+FoxP3+ regulatory T cells (Treg cells) play a protective role against the development and progression of the inflammatory disease atherosclerosis (AS). MicroRNA-21 (miR-21) is expressed in Treg cells and is up-regulated in the context of AS and other inflammatory diseases. AIMS: This study aimed to determine the role of miR-21 in Treg cell regulation and gene expression during the development of AS in patients with coronary heart disease (CHD)...
2015: Cellular Physiology and Biochemistry
Xiao-Feng Lei, Wenguang Fu, Joo-Ri Kim-Kaneyama, Tomokatsu Omoto, Takuro Miyazaki, Bo Li, Akira Miyazaki
BACKGROUND & AIM: Hydrogen peroxide-inducible clone-5 (Hic-5), also named as transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was found to be induced by TGF-β. Previous studies have shown that TGF-β is a principal mediator of hepatic stellate cell (HSC) activation in liver fibrosis. However, this process remains elusive. In this study, we aimed to define the role of Hic-5 in HSC activation and liver fibrosis. METHODS: We examined the expression levels of Hic-5 during HSCs activation and in fibrotic liver tissues by quantitative real-time reverse transcriptase polymerase chain reaction, Western blot and immunohistochemistry...
January 2016: Journal of Hepatology
Thomas Courivaud, Nathalie Ferrand, Abdelouahid Elkhattouti, Santosh Kumar, Laurence Levy, Olivier Ferrigno, Azeddine Atfi, Céline Prunier
Although E3 ubiquitin ligases are deemed to play key roles in normal cell function and homeostasis, whether their alterations contribute to cancer pathogenesis remains unclear. In this study, we sought to investigate potential mechanisms that govern WWP1/Tiul1 (WWP1) ubiquitin ligase activity, focusing on its ability to trigger degradation of TGFβ type I receptor (TβRI) in conjunction with Smad7. Our data reveal that the WWP1 protein is very stable at steady states because its autopolyubiquitination activity is silenced due to an intra-interaction between the C2 and/or WW and Hect domains that favors WWP1 monoubiquitination at the expense of its polyubiquitination or polyubiquitination of TβRI...
August 21, 2015: Journal of Biological Chemistry
Rong-Qi Wang, Hong-Mei Mi, Hui Li, Su-Xian Zhao, Yan-Hong Jia, Yue-Min Nan
OBJECTIVES: Fuzheng Huayu recipe (FZHY) exerts significant protective effects against liver fibrosis by strengthening the body's resistance and removing blood stasis. However, the molecular mechanisms through which FZHY affects liver fibrosis are still unclear. In this study, we examined the expression levels of factors involved in the inhibitor κB kinase-β (IKK-β)/nuclear factor-κB (NF-κB) and transforming growth factor beta 1 (TGF-β1)/Smad signaling pathways to elucidate whether FZHY could attenuate nutritional steatohepatitis and fibrosis in mice...
April 2015: Iranian Journal of Basic Medical Sciences
Zhao-hui Wang, Qi-shun Zhang, Yan-li Duan, Jian-lei Zhang, Guo-fei Li, Dong-lin Zheng
Transforming growth factors β (TGF-β) pathway has been proven to play important roles in oncogenesis and angiogenesis of gliomas. MiR-132 might be related to TGF-β signaling pathway and high miR-132 expression was reported to be a biomarker of poor prognosis in patients diagnosed with glioma. However, the expression regulation way involved in TGF-β pathway and clinical significance of miR-132 have not been investigated in glioma cells. Here we reported that the mRNA level of miR-132 and TGF-β concentration were both increased in patients with brain glioma...
July 31, 2015: Biochemical and Biophysical Research Communications
Yufeng Jiang, Chao Wu, Alex Boye, Jiajun Wu, Jiyu Wang, Xiaochuan Yang, Yan Yang
Mitogen-activated protein kinase (MAPK) pathway-dependent linker phosphorylation of Smad2/3 and subsequent formation of Smad2/3/4 complex and its nuclear translocation are crucial for dysregulated transforming growth factor beta (TGF)-β/Smad signaling in liver fibrosis. Abrogation of this critical step of TGF-β/Smad signaling leading to liver fibrosis could provide new insights for future therapy, but the mechanisms remain incompletely understood. In pursuit, we investigated the subcellular expression and nuclear trafficking of the rate limiting Smad2/3/4 complex in exogenous TGF-β1-stimulated myofibroblasts (MFBs) using three MAPK-specific inhibitors...
August 2015: Molecular and Cellular Biochemistry
Zhiming Zhao, Hao Xi, Dabin Xu, Chenggang Li
Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant. Efficient control of cancer growth may substantially improve the survival of PDAC patients. However, no efficient treatments are so far available. Here, we inhibited transforming growth factor β (TGFβ) receptor signaling by overexpression of a key inhibitor of this pathway, SMAD7, in the mouse pancreas, using a recently developed intraductal infusion method. Overexpression of SMAD7 significantly increased growth of both implanted PDAC and PDAC by K-ras modification...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Guan Wang, Xianfeng Li, Weiping Tian, Yan Wang, Dandan Wu, Zhongsheng Sun, Enfeng Zhao
As a transforming growth factor-β (TGF-β)-inducible gene, the expression of Krüppel-like transcription factor 11 (KLF11) is altered in several types of cancer. In the current study, through using human 9K CpG island array, KLF11 was identified as one of hypermethylated genes in RAS-transformed ovarian T29H cells. Methylation of the KLF11 promoter was also observed in ovarian cancer tissue samples accompanied by significantly reduced KLF11 gene expression. Interestingly, the expression of SMAD2, SMAD3, and SMAD7 genes was reduced in the tumour, whilst no change was found in TGF-β expression...
July 2015: Genes, Chromosomes & Cancer
Xiaolong Tu, Xiuxiu Zheng, Huanan Li, Zhipeng Cao, Hanwen Chang, Shaoyuan Luan, Jie Zhu, Jiangning Chen, Yuhui Zang, Junfeng Zhang
Transforming growth factor beta (TGF-β) is crucial for transdifferentiation of hepatic stellate cells (HSCs) and the blunting of TGF-β signaling in HSCs can effectively prevent liver fibrosis. Krüppel-like factor 11 (KLF11) is an early response transcription factor that potentiates TGF-β/Smad signaling by suppressing the transcription of inhibitory Smad7. Using a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis, we observed significant upregulation of KLF11 in the activated HSCs during liver fibrogenesis...
July 2015: Toxicological Sciences: An Official Journal of the Society of Toxicology
Petra Balogh, Márton Magyar, Arnold Szabó, Nándor Müllner, István Likó, Attila Patócs, Anna L Kiss
We previously showed that intraperitoneal administration of Freund's adjuvant treatment resulted in acute peritonitis and TGF-β was found to be one of the main organizers of the subsequent EMT in mesothelial cells. In the present study, we investigated whether TGF-β signaling molecules are present in mesothelial cells and how their compartmentalization pattern changes with the dynamics of inflammatory events in vivo. In addition, we tried to evaluate the turnover of endosomal compartments concomitant with the internalization of signaling molecules and examine whether caveola-mediated internalization might play a role in the termination of TGF-β signaling...
May 2015: European Journal of Cell Biology
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