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Smad3 AND Beta cells

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https://www.readbyqxmd.com/read/28225655/mnte-2-pyp-treatment-or-nox4-inhibition-protects-against-radiation-induced-damage-in-mouse-primary-prostate-fibroblasts-by-inhibiting-the-tgf-beta-1-signaling-pathway
#1
Arpita Chatterjee, Elizabeth A Kosmacek, Rebecca E Oberley-Deegan
Prostate cancer patients who undergo radiotherapy frequently suffer from side effects caused by radiation-induced damage to normal tissues adjacent to the tumor. Exposure of these normal cells during radiation treatment can result in tissue fibrosis and cellular senescence, which ultimately leads to postirradiation-related chronic complications including urinary urgency and frequency, erectile dysfunction, urethral stricture and incontinence. Radiation-induced reactive oxygen species (ROS) have been reported as the most potent causative factor for radiation damage to normal tissue...
February 22, 2017: Radiation Research
https://www.readbyqxmd.com/read/28108836/smad-dependent-signaling-plays-a-detrimental-role-in-a-fly-model-of-smarcb1-deficiency-and-the-biology-of-atypical-teratoid-rhabdoid-tumors
#2
Astrid Jeibmann, Jacqueline Schulz, Kristin Eikmeier, Pascal D Johann, Katharina Thiel, Isabel Tegeder, Oliver Ambrée, Michael C Frühwald, Stefan M Pfister, Marcel Kool, Werner Paulus, Martin Hasselblatt
Atypical teratoid/rhabdoid tumors (ATRT) are highly malignant brain tumors arising in young children. The majority of ATRT is characterized by inactivation of the chromatin remodeling complex member SMARCB1 (INI1/hSNF5). Little is known, however, on downstream pathways involved in the detrimental effects of SMARCB1 deficiency which might also represent targets for treatment. Using Drosophila melanogaster and the Gal4-UAS system, modifier screens were performed in order to identify the role of SMAD dependent signaling in the lethal phenotype associated with knockdown of snr1, the fly homolog of SMARCB1...
January 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28107544/cutaneous-hpv8-and-mmupv1-e6-proteins-target-the-notch-and-tgf-%C3%AE-tumor-suppressors-to-inhibit-differentiation-and-sustain-keratinocyte-proliferation
#3
Jordan M Meyers, Aayushi Uberoi, Miranda Grace, Paul F Lambert, Karl Munger
Cutaneous beta-papillomaviruses are associated with non-melanoma skin cancers that arise in patients who suffer from a rare genetic disorder, Epidermodysplasia verruciformis (EV) or after immunosuppression following organ transplantation. Recent studies have shown that the E6 proteins of the cancer associated beta human papillomavirus (HPV) 5 and HPV8 inhibit NOTCH and TGF-β signaling. However, it is unclear whether disruption of these pathways may contribute to cutaneous HPV pathogenesis and carcinogenesis...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28039556/microrna-15b-silencing-inhibits-il-1%C3%AE-induced-extracellular-matrix-degradation-by-targeting-smad3-in-human-nucleus-pulposus-cells
#4
Liang Kang, Cao Yang, Huipeng Yin, Kangcheng Zhao, Wei Liu, Wenbin Hua, Kun Wang, Yu Song, Ji Tu, Shuai Li, Rongjin Luo, Yukun Zhang
OBJECTIVES: To determine the role of microRNA-15b (miR-15b) in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation in the nucleus pulposus (NP). RESULTS: MiR-15b was up-regulated in degenerative NP tissues and in IL-1β-stimulated NP cells, as compared to the levels in normal controls (normal tissue specimens from patients with idiopathic scoliosis). Bioinformatics and luciferase activity analyses showed that mothers against decapentaplegic homolog 3 (SMAD3), a key mediator of the transforming growth factor-β signaling pathway, was directly targeted by miR-15b...
December 30, 2016: Biotechnology Letters
https://www.readbyqxmd.com/read/27906182/bcl-3-regulates-tgf%C3%AE-signaling-by-stabilizing-smad3-during-breast-cancer-pulmonary-metastasis
#5
Xi Chen, Xinwei Cao, Xiaohua Sun, Rong Lei, Pengfei Chen, Yongxu Zhao, Yuhang Jiang, Jie Yin, Ran Chen, Deji Ye, Qi Wang, Zhanjie Liu, Sanhong Liu, Chunyan Cheng, Jie Mao, Yingyong Hou, Mingliang Wang, Ulrich Siebenlist, Y Eugene Chin, Ying Wang, Liu Cao, Guohong Hu, Xiaoren Zhang
Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27880821/inhibition-of-the-tgf%C3%AE-pathway-enhances-retinal-regeneration-in-adult-zebrafish
#6
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
https://www.readbyqxmd.com/read/27835939/anti-fibrotic-action-of-pirfenidone-in-dupuytren-s-disease-derived-fibroblasts
#7
Chaoming Zhou, Fang Liu, Phillip H Gallo, Mark E Baratz, Sandeep Kathju, Latha Satish
BACKGROUND: Dupuytren's disease (DD) is a complex fibro-proliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers. Transforming growth factor beta (TGF-β1) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in DD. Pirfenidone (PFD) is an active small molecule shown to inhibit TGF-β1-mediated action in other fibrotic disorders. This study investigates the efficacy of PFD in vitro in inhibiting TGF-β1-mediated cellular functions leading to Dupuytren's fibrosis...
November 11, 2016: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/27703224/gallic-acid-prevents-isoproterenol-induced-cardiac-hypertrophy-and-fibrosis-through-regulation-of-jnk2-signaling-and-smad3-binding-activity
#8
Yuhee Ryu, Li Jin, Hae Jin Kee, Zhe Hao Piao, Jae Yeong Cho, Gwi Ran Kim, Sin Young Choi, Ming Quan Lin, Myung Ho Jeong
Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27696331/tgf-beta-receptor-mediated-telomerase-inhibition-telomere-shortening-and-breast-cancer-cell-senescence
#9
Lucy Cassar, Craig Nicholls, Alex R Pinto, Ruping Chen, Lihui Wang, He Li, Jun-Ping Liu
Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis...
January 2017: Protein & Cell
https://www.readbyqxmd.com/read/27683263/smad3-activation-a-converging-point-of-dysregulated-tgf-beta-superfamily-signaling-and-genetic-aberrations-in-granulosa-cell-tumor-development
#10
Xin Fang, Yang Gao, Qinglei Li
Ovarian granulosa cell tumors (GCTs) are rare gynecologic tumors in women. Due to the rarity and limited research efforts invested, the etiology of GCTs remains poorly defined. A landmark study has discovered the mutation of forkhead box L2 (FOXL2) as a genetic hallmark of adult GCTs in the human. However, our understanding of the role of cell signaling in GCT development is far from complete. Increasing lines of evidence highlight the importance of TGF-beta (TGFB) superfamily signaling in the pathogenesis of GCTs...
November 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27633729/anti-hepatic-fibrosis-effects-of-a-novel-turtle-shell-decoction-by-inhibiting-hepatic-stellate-cell-proliferation-and-blocking-tgf-%C3%AE-1-smad-signaling-pathway-in-rats
#11
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
https://www.readbyqxmd.com/read/27626488/tgf-%C3%AE-1-promotes-colorectal-cancer-immune-escape-by-elevating-b7-h3-and-b7-h4-via-the-mir-155-mir-143-axis
#12
Xinru Zhou, Yong Mao, Jianjie Zhu, Fanyi Meng, Qi Chen, Lihua Tao, Rui Li, Fengqing Fu, Cuiping Liu, Yuanjia Hu, Weipeng Wang, Hongjian Zhang, Dong Hua, Weichang Chen, Xueguang Zhang
Transforming growth factor-beta 1 (TGF-β1) suppresses T cell function, promoting tumor immune escape. Yet, whether the depression of TGF-β1 on T cell function is mediated by co-inhibitory molecules B7-H3 and B7-H4 remains largely unclear. Here, we demonstrated that TGF-β1 elevated the expression of miR-155 in colorectal cancer cells through SMAD3 and SMAD4. The upregulated miR-155 attenuated miR-143 by inhibiting its direct target, the transcription factor CEBPB. Consequently, the direct target genes of miR-143, B7-H3 and B7-H4, were augmented in the cytoplasm and membrane of tumor cells...
11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27522058/sirtuin-3-deregulation-promotes-pulmonary-fibrosis
#13
Meredith L Sosulski, Rafael Gongora, Carol Feghali-Bostwick, Joseph A Lasky, Cecilia G Sanchez
Oxidative stress leads to alveolar epithelial cell injury and fibroblast-myofibroblast differentiation (FMD), key events in the pathobiology of pulmonary fibrosis (PF). Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase regulator of antioxidant response and mitochondrial homeostasis. Here, we demonstrate reduced SIRT3 expression in the lungs of old mice compared to young mice, as well as in two murine models of PF. The analysis of the pattern of SIRT3 expression in the lungs of patients with PF revealed low SIRT3 staining within the fibrotic regions...
August 13, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27462075/transforming-growth-factor-%C3%AE-tgf-%C3%AE-inhibits-the-expression-of-factor-vii-activating-protease-fsap-in-hepatocytes
#14
Silke Leiting, Sebastian Seidl, Adoracion Martinez-Palacian, Lars Muhl, Sandip M Kanse
Deletion of the Habp2 gene encoding Factor VII-activating protease (FSAP) increases liver fibrosis in mice. A single nucleotide polymorphism (G534E) in HABP2 leads to lower enzymatic activity and is associated with enhanced liver fibrosis in humans. Liver fibrosis is associated with a decrease in FSAP expression but, to date, nothing is known about how this might be regulated. Primary mouse hepatocytes or the hepatocyte cell line, AML12, were treated with different factors, and expression of FSAP was determined...
September 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27452523/rewiring-of-the-apoptotic-tgf-%C3%AE-smad-nf%C3%AE%C2%BAb-pathway-through-an-oncogenic-function-of-p27-in-human-papillary-thyroid-cancer
#15
A R Garcia-Rendueles, J S Rodrigues, M E R Garcia-Rendueles, M Suarez-Fariña, S Perez-Romero, F Barreiro, I Bernabeu, J Rodriguez-Garcia, L Fugazzola, T Sakai, F Liu, J Cameselle-Teijeiro, S B Bravo, C V Alvarez
Papillary thyroid carcinoma (PTC), the most frequent thyroid cancer, is characterized by low proliferation but no apoptosis, presenting frequent lymph-node metastasis. Papillary thyroid carcinoma overexpress transforming growth factor-beta (TGF-β). In human cells, TGF-β has two opposing actions: antitumoral through pro-apoptotic and cytostatic activities, and pro-tumoral promoting growth and metastasis. The switch converting TGF-β from a tumor-suppressor to tumor-promoter has not been identified. In the current study, we have quantified a parallel upregulation of TGF-β and nuclear p27, a CDK2 inhibitor, in samples from PTC...
July 25, 2016: Oncogene
https://www.readbyqxmd.com/read/27411504/microrna-181a-5p-enhances-cell-proliferation-in-medullary-thymic-epithelial-cells-via-regulating-tgf-%C3%AE-signaling
#16
Dongguang Guo, Yaqiong Ye, Junjie Qi, Lihua Zhang, Lifeng Xu, Xiaotong Tan, Xiaofang Yu, Qihong Liu, Jilong Liu, Yuan Zhang, Yongjiang Ma, Yugu Li
The expression profiles of miRNAs in thymus tissues from mice of different age have been demonstrated in our previous study. After an integrated analysis of the miRNA expression profiles, we demonstrated that the expression of miR-181a-5p was significantly decreased in thymic epithelial cells (TECs) from 10- to 19-month-old mice when compared with that in TECs from 1-month-old mice by quantitative reverse transcriptase polymerase chain reaction. We hypothesized that miR-181a-5p in TECs might be associated with the age-related thymus involution through regulating some genes or signaling pathway...
September 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27301199/electrospun-polyacrylonitrile-based-nanofibers-maintain-embryonic-stem-cell-stemness-via-tgf-beta-signaling
#17
Shih-Ping Liu, Chen-Huan Lin, Shao-Ji Lin, Ru-Huei Fu, Yu-Chuen Huang, Shih-Yin Chen, Shinn-Zong Lin, Chung Y Hsu, Woei-Cherng Shyu
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are capable of self-renewal and differentiation into any cell type, thus making them the focus of many clinical application studies. Culturing ESCs on mouse embryonic fibroblast-derived and cell-based feeder layers to maintain pluripotency is a standard laboratory procedure. However, xenogeneic contamination and the large amount of time required for feeder cell preparation are two challenges that encourage the use of a murine-based feeder layer...
April 2016: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/27105914/high-glucose-induced-matrilin-2-expression-in-mouse-mesangial-cells-was-mediated-by-transforming-growth-factor-beta-1-tgf-%C3%AE-1
#18
Shukun Zhang, Menglan Zhang, Hong Huang, Shiying Zhou, Yanshneg Du, Xin Yi, Junming Luo
This study aimed at evaluating the effect of high glucose on the expression of extracellular matrix (ECM) protein Matrilin-2 and the mechanism underlying this effect by using a mouse mesangial cell line. Mouse mesangial cells (MMCs) were cultured in media containing normal (5 mM d-glucose) or high concentrations of glucose (30 mM d-glucose). The expression of Matrilin-2 was assessed by either RT-PCR or western blot. Additionally, transforming growth factor beta 1 (TGF-β1) inhibitors and TGF-β1 were used to determine whether glucose-regulated Matrilin-2 expression was mediated by the TGF-β1/Smad3 signaling pathway...
May 27, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27073729/p53-is-required-for-doxorubicin-induced-apoptosis-via-the-tgf-beta-signaling-pathway-in-osteosarcoma-derived-cells
#19
Yifu Sun, Peng Xia, Haipeng Zhang, Biao Liu, Ying Shi
Osteosarcoma is the most common type of aggressive bone cancer. Current treatment strategies include surgical resection, radiation, and chemotherapy. Doxorubicin has been widely used as a chemotherapeutic drug to treat osteosarcoma. However, drug resistance has become a challenge to its use. In this study, p53-wild type U2OS and p53-null MG-63 osteosarcoma-derived cells were used to investigate the mechanism of doxorubicin-induced cytotoxicity. In cell viability assays, doxorubicin effectively induced apoptosis in U2OS cells via the p53 signaling pathway, evidenced by elevated PUMA and p21 protein levels and activated caspase 3 cleavage...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27059791/toll-like-receptor-3-mediates-prominin-1-expressing-cell-expansion-in-biliary-atresia-via-transforming-growth-factor-beta
#20
Jessica A Zagory, Marie V Nguyen, William Dietz, Nirmala Mavila, Allison Haldeman, Anatoly Grishin, Kasper S Wang
BACKGROUND: In biliary atresia (BA), epithelial-mesenchymal hepatic progenitor cells (HPC) expressing the stem/progenitor cell marker PROMININ-1 (PROM1) undergo expansion and subsequent transdifferentiation into collagen-producing myofibroblasts within regions of evolving biliary fibrosis under the regulation of Transforming Growth Factor-β (TGFβ) signaling. We hypothesized that pro-inflammatory Toll-like Receptor-3 (TLR3) signal activation promotes the differentiation of PROM1+ HPC via TGFβ pathway activation in vitro...
June 2016: Journal of Pediatric Surgery
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