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Smad7 AND TGF beta

Shimaa Saad El-Din, Hanan Fouad, Laila Ahmed Rashed, Soheir Mahfouz, Rania Elsayed Hussein
Background: Transforming growth factor-beta (TGF-β) signaling is recognized as being critical for carcinogenesis. Vitamin D has proved to exert numerous tumor suppressive effects. Effects of bone marrow derived mesenchymal stem cells (BM-MSCs) on tumor progression are still controversial. The present study was conducted to evaluate the effects of BM-MSCs and vitamin D on TGF-β signaling in an experimental hepatocellular carcinoma (HCC) model in rats. Materials and Methods: The study was conducted on fifty female white albino rats divided equally into 5 groups: controls, HCC induced by diethyl-nitrosamine (DENA) and carbon tetrachloride (CCl4), HCC plus MSCs, HCC plus vitamin D and HCC plus both MSCs and vitamin D...
April 25, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Yong-Guo Zhang, Megha Singhal, Zhijie Lin, Christopher Manzella, Anoop Kumar, Waddah A Alrefai, Pradeep K Dudeja, Seema Saksena, Jun Sun, Ravinder K Gill
Salmonella and Citrobacter are gram negative, members of Enterobacteriaceae family that are important causative agents of diarrhea and intestinal inflammation. TGF-β1 is a pleiotropic multifunctional cytokine that has been implicated in modulating the severity of microbial infections. How these pathogens alter the TGF-β1 signaling pathways in the intestine is largely unknown. Streptomycin-pretreated C57BL/6J mouse model colonized with S. typhimurium for 8 hours (acute) and 4 days (chronic) infection and FVB/N mice infected with C...
January 30, 2018: Gut Microbes
Menno Evert Groeneveld, Natalija Bogunovic, René John Philip Musters, Geert Jan Tangelder, Gerard Pals, Willem Wisselink, Dimitra Micha, Kak Khee Yeung
BACKGROUND: Marfan syndrome (MFS), a congenital connective tissue disorder leading to aortic aneurysm development, is caused by fibrillin-1 (FBN1) gene mutations. Transforming growth factor beta (TGF-β) might play a role in the pathogenesis. It is still a matter of discussion if and how TGF-β up-regulates the intracellular downstream pathway, although TGF-β receptor 3 (TGFBR3 or Betaglycan) is thought to be involved. We aimed to elucidate the role of TGFBR3 protein in TGF-β signaling in Marfan patients...
January 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Shatakshee Chatterjee, Srikant Prasad Verma, Priyanka Pandey
PURPOSE: Initiation and progression of fluid filled cysts mark Autosomal Dominant Polycystic Kidney Disease (ADPKD). Thus, improved therapeutics targeting cystogenesis remains a constant challenge. Microarray studies in single ADPKD animal models species with limited sample sizes tend to provide scattered views on underlying ADPKD pathogenesis. Thus we aim to perform a cross species meta-analysis to profile conserved biological pathways that might be key targets for therapy. METHODS: Nine ADPKD microarray datasets on rat, mice and human fulfilled our study criteria and were chosen...
September 5, 2017: Gene
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
Li Zhang, Jie Gao, Sheng Cui
Substantive evidence has indicated that the sympathetic innervation contributes to the regulation and development of ovarian functions. Norepinephrine (NE) is one of the major neurotransmitters contained in the extrinsic ovarian sympathetic nerves and is thought to be a potent moderator of ovarian functions such as steroidogenesis and granulosa cell proliferation or apoptosis. However, the mechanisms of NE regulation of granulosa cell apoptosis in the rat ovary are rare. Real-time PCR and Western blot results show that NE regulates the expression of miR-21 in primary granulosa cells in a dose-dependent manner...
May 2017: Journal of Molecular Endocrinology
Rachel K Patel, Nithisha Prasad, Ram Kuwar, Debanjan Haldar, P M Abdul-Muneer
Mild traumatic brain injury (mTBI) is a low-level injury, which often remains undiagnosed, and in most cases it leads to death and disability as it advances as secondary injury. Therefore, it is important to study the underlying signaling mechanisms of mTBI-associated neurological ailments. While transforming growth factor-beta1 (TGF-β1) has a significant role in inflammation and apoptosis in myriads of other pathophysiological conditions, the precise function of increased TGF-β1 after mTBI is unknown. In this study, our objective is to study the physiological relevance and associated mechanisms of TGF-β1-mediated inflammation and apoptosis in mTBI...
April 19, 2017: Brain, Behavior, and Immunity
Zhi-Cheng Hu, Fen Shi, Peng Liu, Jian Zhang, Dong Guo, Xiao-Ling Cao, Chu-Fen Chen, Shan-Qiang 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 TIEG1 is markedly higher in keloid fibroblasts, whereas protein, mRNA, and promoter activity levels of Smad7 are decreased. When TIEG1 was knocked down with small interfering RNA, both the promoter activity and protein expression of Smad7 were increased, whereas collagen production and the proliferation, migration, and invasion of keloid fibroblasts were decreased...
May 2017: Journal of Investigative Dermatology
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
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...
November 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
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