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https://www.readbyqxmd.com/read/27903972/gdf15-contributes-to-radioresistance-and-cancer-stemness-of-head-and-neck-cancer-by-regulating-cellular-reactive-oxygen-species-via-a-smad-associated-signaling-pathway
#1
Yan-Liang Li, Joseph T Chang, Li-Yu Lee, Kang-Hsing Fan, Ya-Ching Lu, Yi-Chen Li, Chang-Hsu Chiang, Guo-Rung You, Hsin-Ying Chen, Ann-Joy Cheng
Radiotherapy is an integral part for the treatment of head and neck cancer (HNC), while radioresistance is a major cause leads to treatment failure. GDF15, a member of the TGF-β superfamily, is hypothesized to participate in various types of homeostasis. However, the potential role of this molecule in regulation of radiosensitivity remains unclear. In this study, we demonstrated that GDF15 contributed to radioresistance of HNC, as determined by both gain- and lost-of-functional experiments. These results were achieved by the induction of mitochondrial membrane potential and suppression of intracellular reactive oxygen species (ROS)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903526/hepcidin-upregulation-by-inflammation-is-independent-of-smad1-5-8-signaling-by-activin-b
#2
Céline Besson-Fournier, Aurélie Gineste, Chloé Latour, Ophélie Gourbeyre, Delphine Meynard, Patricia Martin, Eric Oswald, Hélène Coppin, Marie-Paule Roth
No abstract text is available yet for this article.
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27883221/alcohol-exposure-causes-overexpression-of-heart-development-related-genes-by-affecting-the-histone-h3-acetylation-via-bmp-signaling-pathway-in-cardiomyoblast-cells
#3
Jin Shi, Weian Zhao, Bo Pan, Min Zheng, Lina Si, Jing Zhu, Lingjuan Liu, Jie Tian
BACKGROUND: Abusive alcohol utilization of pregnant woman may cause congenital heart disease (CHD) of fetus, where alcohol ignites histone H3 hyperacetylation leading to abnormal development of heart morphogenesis and associated genes. Knowledge about the regularized upstream genes is little, but bone morphogenetic protein (BMP) signaling may actively and prominently take part in alteration in acetylation of histone H3. The supreme objective of this study was to unearth the involvement of BMP signaling pathway in alcohol-driven hyperacetylation of histone H3 in cardiomyoblast cells...
November 24, 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27881195/the-involvement-of-runx2-and-sparc-genes-in-the-bacterial-chondronecrosis-with-osteomyelitis-in-broilers
#4
E Paludo, A M G Ibelli, J O Peixoto, F C Tavernari, C A V Lima-Rosa, J R C Pandolfi, M C Ledur
Economic losses due to an increase of leg disorders in broilers have become a major concern of the poultry industry. Despite the efforts to reduce skeletal abnormalities in chickens, insufficient progress has been made. Bacterial chondronecrosis with osteomyelitis (BCO) is one of the main disorders that affect bone integrity in broilers. However, the genetic pathways and genes involved in most bone problems, including BCO, remains unclear. In this study, femoral samples from male broilers with 45 days of age affected or not with BCO were used to compare the relative expression with a reverse transcription real time PCR approach of 13 candidate genes: SPP1 (osteopontin), TNFRSF11B (osteoprotegerin), SPARC (osteonectin), CALB1 (calbidin 1), CALM (Calmodulin 2), IBSP (sialoprotein), COL1A2 (collagen, type I, α 2), BMP2 (bone morphogenetic protein 2), BMP3 (bone morphogenetic protein 3), RANKL (κ-B nuclear factor ligand), SMAD1 (SMAD family member 1), LEPR (leptin receptor) and RUNX2 (related transcription factor Runt 2)...
November 24, 2016: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/27875556/mxa-is-a-novel-regulator-of-endosome-associated-transcriptional-signaling-by-bone-morphogenetic-proteins-4-and-9-bmp4-and-bmp9
#5
Huijuan Yuan, Pravin B Sehgal
There is confusion about the role that IFN-α plays in the pathogenesis of pulmonary arterial hypertension (PAH) with different investigators reporting a causative or a protective role. There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2. In the present study, we investigated MxA, an IFN-α-inducible cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in the presence of PAH-disease-associated mutants of BMPR2...
2016: PloS One
https://www.readbyqxmd.com/read/27872076/anti-schistosomiasis-liver-fibrosis-effects-of-chlorogenic-acid-through-il-13-mir-21-smad7-signaling-interactions-in-vivo-and-in-vitro
#6
Yao Wang, Fan Yang, Jun Xue, Xuan Zhou, Lei Luo, Qian Ma, Yun-Fei Chen, Juan Zhang, Shu-Ling Zhang, Lei Zhao
This study is to investigate the anti-Schistosomiasis liver fibrosis effects of chlorogenic acid (CGA) on IL-13/miR-21/Smad7 signaling interactions in hepatic stellate LX2 cell line and Schistosome-infected mice. The transfection was based on the GV273-miR-21-EGFP and GV369-miR-21-EGFP lentiviral system to up- or down-regulate miR-21 gene in LX2 cells. The mRNA expression of miR-21, Smad7 and connective tissue growth factor (CTGF) and protein expression of Smad7, CTGF, Smad1, p-Smad1, Smad2, p-Smad2, Smad2/3, p-Smad2/3, TGF-β receptor I and α-SMA were assayed...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27866969/overexpression-of-cd109-in-the-epidermis-differentially-regulates-alk1-versus-alk5-signaling-and-modulates-extracellular-matrix-synthesis-in-the-skin
#7
Joshua Vorstenbosch, Christopher M Nguyen, Shufeng Zhou, You Jung Seo, Aya Siblini, Kenneth W Finnson, Albane A Bizet, Simon D Tran, Anie Philip
Transforming growth factor-beta (TGF-β) is a multifunctional growth factor involved in many physiological processes including wound healing and inflammation. Excessive TGF-β signaling in the skin has been implicated in fibrotic skin disorders such as keloids and scleroderma. We have previously identified CD109 as a TGF- β co-receptor and inhibitor of TGF-ß signaling, and have shown that transgenic mice overexpressing CD109 in the epidermis display decreased scarring. In certain cell types, in addition to the canonical type I receptor, ALK5 which activates Smad2/3, TGF-β can signal through another type I receptor ALK1 which activates Smad1/5...
November 17, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27864336/bmp4-promotes-mouse-ips-cell-differentiation-to-male-germ-cells-via-smad1-5-gata4-id1-and-id2
#8
Shi Yang, Qingqing Yuan, Minghui Niu, Jingmei Hou, Zijue Zhu, Min Sun, Zheng Li, Zuping He
Generation of male germ cells from pluripotent cells could provide male gametes for treating male infertility and offer an ideal model for unveiling molecular mechanisms of spermatogenesis. However, the influence and exact molecular mechanisms, especially downstream effectors of BMP4 signaling pathways, in male germ cell differentiation of the induce pluripotent stem (iPS) cells, remain unknown. This study was designed to explore the role and mechanism of BMP4 signaling in the differentiation of mouse induced pluripotent stem (iPS) cells to male germ cells...
November 18, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27856416/regulation-and-function-of-bone-morphogenetic-protein-signaling-in-colonic-injury-and-inflammation
#9
Tuo Ji, Hidehiko Takabayashi, Maria Mao, Xu Han, Xiang Xue, Jennifer C Brazil, Kathryn A Eaton, Yatrik M Shah, Andrea Todisco
The bone morphogenetic proteins (BMPs) regulate gastrointestinal homeostasis. We investigated the expression of BMP-4 and the localization and function of BMP signaling during colonic injury and inflammation. Wild type mice and mice expressing the β-galactosidase (β-gal) gene under the control of a BMP responsive element (BRE), BMP-4-β-gal/+ mice, and animals generated by crossing villin-Cre mice to mice with floxed alleles of BMP receptor 1A (villin-Cre;Bmpr1a(flox/flox)), were treated with DSS to induce colonic injury and inflammation...
November 17, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27856249/the-transcriptional-modulator-ifrd1-is-a-negative-regulator-of-bmp-2-dependent-osteoblastogenesis
#10
Yuki Onishi, Gyujin Park, Takashi Iezaki, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Kakeru Ozaki, Eiichi Hinoi
We previously demonstrated that the transcriptional coactivator/repressor interferon-related developmental regulator 1 (Ifrd1) was expressed in osteoblasts and participated in the regulation of bone homeostasis. However, it remains unclear how Ifrd1 expression itself is regulated in osteoblasts. In the present study, we investigated the upstream regulatory mechanisms of Ifrd1 in osteoblasts during osteoblastogenesis. Ifrd1 protein expression and runt-related transcription factor 2, the master regulator of osteoblastogenesis, were markedly upregulated by bone morphogenetic protein 2 (BMP-2) stimulation in primary osteoblasts...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27848974/differential-expression-of-tgf-%C3%AE-superfamily-members-and-role-of-smad1-5-9-signalling-in-chondral-versus-endochondral-chondrocyte-differentiation
#11
Verena Dexheimer, Jessica Gabler, Katharina Bomans, Tanja Sims, Georg Omlor, Wiltrud Richter
Proteins of the transforming-growth-factor-β (TGF-β)-superfamily have a remarkable ability to induce cartilage and bone and the crosstalk of TGF-β - and BMP-signalling pathways appears crucial during chondrocyte development. Aim was to assess the regulation of TGF-β-superfamily members and of Smad2/3- and Smad1/5/9-signalling during endochondral in vitro chondrogenesis of mesenchymal stromal cells (MSC) relative to chondral redifferentiation of articular chondrocytes (AC) to adjust chondrocyte development of MSC towards a less hypertrophic phenotype...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27834400/notch-regulates-bmp-responsiveness-and-lateral-branching-in-vessel-networks-via-smad6
#12
Kevin P Mouillesseaux, David S Wiley, Lauren M Saunders, Lyndsay A Wylie, Erich J Kushner, Diana C Chong, Kathryn M Citrin, Andrew T Barber, Youngsook Park, Jun-Dae Kim, Leigh Ann Samsa, Jongmin Kim, Jiandong Liu, Suk-Won Jin, Victoria L Bautch
Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation...
November 11, 2016: Nature Communications
https://www.readbyqxmd.com/read/27829314/bone-morphogenetic-protein-2-but-not-mesenchymal-stromal-cells-exert-regenerative-effects-on-canine-and-human-nucleus-pulposus-cells
#13
Frances Bach, Alberto Miranda-Bedate, Ferdi van Heel, Frank Riemers, Margot Muller, Laura Creemers, Keita Ito, Karin Benz, Björn Meij, M Tryfonidou
Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2 (BMP2) on canine and human chondrocyte-like cells (CLCs) derived from the nucleus pulposus of degenerated IVDs were studied. Human and canine CLCs were cultured in 3D micro-aggregates in basal culture medium supplemented with/without TGF-β1 (10 ng/mL) or BMP2 (100 or 250 ng/mL)...
November 9, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27815243/bmp4-acts-as-a-dorsal-telencephalic-morphogen-in-a-mouse-embryonic-stem-cell-culture-system
#14
Momoko Watanabe, Ernest S Fung, Felicia B Chan, Jessica S Wong, Margaret Coutts, Edwin S Monuki
The concept of a morphogen - a molecule that specifies two or more cell fates in a concentration-dependent manner - is paradigmatic in developmental biology. Much remains unknown, however, about the existence of morphogens in the developing vertebrate CNS, including the mouse dorsal telencephalic midline (DTM). Bone Morphogenetic Proteins (BMPs) are candidate DTM morphogens, and our previous work demonstrated BMP4 sufficiency to induce one DTM cell fate - that of choroid plexus epithelial cells (CPECs) - in a mouse embryonic stem cell (mESC) culture system...
November 4, 2016: Biology Open
https://www.readbyqxmd.com/read/27800612/direct-delivery-of-recombinant-pin1-protein-rescued-osteoblast-differentiation-of-pin1-deficient-cells
#15
Woo-Jin Kim, Rabia Islam, Bong-Soo Kim, Young-Dan Cho, Won-Joon Yoon, Jeong-Hwa Baek, Kyung-Mi Woo, Hyun-Mo Ryoo
Pin1 is a peptidyl prolyl cis-trans isomerase that specifically binds to the phosphoserine-proline or phosphothreonine-proline motifs of several proteins. We reported that Pin1 plays a critical role in the fate determination of Smad1/5, Runx2 and β-catenin that are indispensable nuclear proteins for osteoblast differentiation. Though several chemical inhibitors has been discovered for Pin1, no activator has been reported as of yet. In this study, we directly introduced recombinant Pin1 protein successfully into the cytoplasm via fibroin nanoparticle encapsulated in cationic lipid...
November 1, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27794120/bmp-smad-id-promotes-reprogramming-to-pluripotency-by-inhibiting-p16-ink4a-dependent-senescence
#16
Yohei Hayashi, Edward C Hsiao, Salma Sami, Mariselle Lancero, Christopher R Schlieve, Trieu Nguyen, Koyori Yano, Ayako Nagahashi, Makoto Ikeya, Yoshihisa Matsumoto, Ken Nishimura, Aya Fukuda, Koji Hisatake, Kiichiro Tomoda, Isao Asaka, Junya Toguchida, Bruce R Conklin, Shinya Yamanaka
Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling. Contrary to a previous study, here we show that FOP fibroblasts showed an increased efficiency of induced pluripotent stem cell (iPSC) generation. This positive effect was attenuated by inhibitors of BMP-SMAD signaling (Dorsomorphin or LDN1931890) or transducing inhibitory SMADs (SMAD6 or SMAD7). In normal fibroblasts, the efficiency of iPSC generation was enhanced by transducing mutant ACVR1 (617G > A) or SMAD1 or adding BMP4 protein at early times during the reprogramming...
October 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27784791/an-affinity-directed-protein-missile-system-for-targeted-proteolysis
#17
Luke J Fulcher, Thomas Macartney, Polyxeni Bozatzi, Annika Hornberger, Alejandro Rojas-Fernandez, Gopal P Sapkota
The von Hippel-Lindau (VHL) protein serves to recruit the hypoxia-inducible factor alpha (HIF1α) protein under normoxia to the CUL2 E3 ubiquitin ligase for its ubiquitylation and degradation through the proteasome. In this report, we modify VHL to engineer an affinity-directed protein missile (AdPROM) system to direct specific endogenous target proteins for proteolysis in mammalian cells. The proteolytic AdPROM construct harbours a cameloid anti-green fluorescence protein (aGFP) nanobody that is fused to VHL for either constitutive or tetracycline-inducible expression...
October 2016: Open Biology
https://www.readbyqxmd.com/read/27758858/enhancer-of-zeste-homolog-2-inhibition-stimulates-bone-formation-and-mitigates-bone-loss-caused-by-ovariectomy-in-skeletally-mature-mice
#18
Amel Dudakovic, Emily T Camilleri, Scott M Riester, Christopher R Paradise, Martina Gluscevic, Thomas M O'Toole, Roman Thaler, Jared M Evans, Huihuang Yan, Malayannan Subramaniam, John R Hawse, Gary S Stein, Martin A Montecino, Meghan E McGee-Lawrence, Jennifer J Westendorf, Andre J van Wijnen
Perturbations in skeletal development and bone degeneration may result in reduced bone mass and quality, leading to greater fracture risk. Bone loss is mitigated by bone protective therapies, but there is a clinical need for new bone-anabolic agents. Previous work has demonstrated that Ezh2 (enhancer of zeste homolog 2), a histone 3 lysine 27 (H3K27) methyltransferase, suppressed differentiation of osteogenic progenitors. Here, we investigated whether inhibition of Ezh2 can be leveraged for bone stimulatory applications...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27754866/transcriptomic-analysis-reveals-novel-transcription-factors-associated-with-renin-angiotensin-aldosterone-system-in-human-atheroma
#19
Ali Nehme, Catherine Cerutti, Kazem Zibara
Despite the well-known role of the renin-angiotensin-aldosterone system (RAAS) in atheroma, its global local organization is poorly understood. In this study, we used transcriptomic meta-analysis to reveal the local transcriptional organization and regulation of 37 extended RAAS (extRAAS) genes in atheroma. Expression analysis and hierarchical clustering were done on extRAAS genes in 32 paired early and advanced atherosclerotic lesions. Contrary to receptor-coding transcripts, multiple angiotensin-metabolizing enzymes showed higher expression in advance, in comparison to early lesions...
October 17, 2016: Hypertension
https://www.readbyqxmd.com/read/27740625/long-term-exposure-to-bisphenol-a-or-benzo-a-pyrene-alters-the-fate-of-human-mammary-epithelial-stem-cells-in-response-to-bmp2-and-bmp4-by-pre-activating-bmp-signaling
#20
Flora Clément, Xinyi Xu, Caterina F Donini, Alice Clément, Soleilmane Omarjee, Emmanuel Delay, Isabelle Treilleux, Béatrice Fervers, Muriel Le Romancer, Pascale A Cohen, Véronique Maguer-Satta
Bone morphogenetic protein 2 (BMP2) and BMP4 are key regulators of the fate and differentiation of human mammary epithelial stem cells (SCs), as well as of their niches, and are involved in breast cancer development. We established that MCF10A immature mammary epithelial cells reliably reproduce the BMP response that we previously identified in human primary epithelial SCs. In this model, we observed that BMP2 promotes luminal progenitor commitment and expansion, whereas BMP4 prevents lineage differentiation...
October 14, 2016: Cell Death and Differentiation
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