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https://www.readbyqxmd.com/read/29154973/inhibition-of-bmp-signaling-overcomes-acquired-resistance-to-cetuximab-in-oral-squamous-cell-carcinomas
#1
Jinlong Yin, Ji-Eun Jung, Sun Il Choi, Sung Soo Kim, Young Taek Oh, Tae-Hoon Kim, Eunji Choi, Sun Joo Lee, Hana Kim, Eun Ok Kim, Yu Sun Lee, Hee Jin Chang, Joo Yong Park, Yeejeong Kim, Tak Yun, Kyun Heo, Youn-Jae Kim, Hyunggee Kim, Yun-Hee Kim, Jong Bae Park, Sung Weon Choi
Despite expressing high levels of the epidermal growth factor receptor (EGFR), a majority of oral squamous cell carcinoma (OSCC) patients show limited response to cetuximab and ultimately develop drug resistance. However, mechanism underlying cetuximab resistance in OSCC is not clearly understood. Here, using a mouse orthotopic xenograft model of OSCC, we show that BMP7-p-Smad1/5/8 signaling contributes to cetuximab resistance. Tumor cells isolated from the recurrent cetuximab-resistant xenograft models exhibited low EGFR expression but extremely high levels of phosphorylated Smad-1, -5, and -8 (p-Smad1/5/8)...
November 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29128220/identification-of-potential-embryokines-in-the-bovine-reproductive-tract
#2
P Tríbulo, L G B Siqueira, L J Oliveira, T Scheffler, P J Hansen
Knowledge of the molecules used by the maternal reproductive tract to regulate development of the preimplantation embryo is largely incomplete. The goal of the present experiment was to identify candidates for this function. The approach was to assess expression patterns in the endometrium and oviduct of 93 genes encoding for hormones, growth factors, chemokines, cytokines, and WNT-related molecules. Results show that all of the genes were expressed in the reproductive tract. Expression in oviduct was affected by day of the estrous cycle for 21 genes with 11 genes having highest expression at estrus (CCL21, CTGF, CXCL10, CXCL16, DKK3, FGF10, IL18, IL33, IL34, PGF, and SFRP2), one gene at d 3 (WNT4), 8 at d 5 (BMP7, HGF, IL6, SFRP1, TGFB1, WIF1, WNT2, and WNT5A), and one at d 7 (IK)...
November 8, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29081505/serotonin-prevents-differentiation-into-brown-adipocytes-and-induces-trans-differentiation-into-white-adipocytes
#3
S Rozenblit-Susan, N Chapnik, O Froy
BACKGROUND/OBJECTIVES: Serotonin is synthesized by many cells in the periphery to affect vasoconstriction, intestinal motility, and glucose and lipid metabolism. It has recently been shown that serotonin leads to fat accumulation in white adipose tissue (WAT). However, the direct effect of serotonin on adipose tissue (BAT) differentiation and metabolism is limited. Therefore, our aim was to investigate the effect of serotonin on brown adipocyte metabolism and differentiation. METHODS: Non-differentiated HIB1B cells and differentiated HIB1B brown adipocytes were treated with serotonin and their metabolism and differentiation examined...
October 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29066944/a-polymer-physics-investigation-of-the-architecture-of-the-murine-orthologue-of-the-7q11-23-human-locus
#4
REVIEW
Andrea M Chiariello, Andrea Esposito, Carlo Annunziatella, Simona Bianco, Luca Fiorillo, Antonella Prisco, Mario Nicodemi
In the last decade, the developments of novel technologies, such as Hi-C or GAM methods, allowed to discover that chromosomes in the nucleus of mammalian cells have a complex spatial organization, encompassing the functional contacts between genes and regulators. In this work, we review recent progresses in chromosome modeling based on polymer physics to understand chromatin structure and folding mechanisms. As an example, we derive in mouse embryonic stem cells the full 3D structure of the Bmp7 locus, a genomic region that plays a key role in osteoblastic differentiation...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29064586/a-pivotal-role-of-ampk-signaling-in-medicarpin-mediated-formation-of-brown-and-beige-adipocytes-from-c3h10t1-2-mesenchymal-stem-cells
#5
Khan Mohammad Imran, Dahyeon Yoon, Yong-Sik Kim
Obesity poses a substantial threat of a worldwide epidemic and requires better understanding of adipose-tissue biology as well as necessitates research into the etiology and therapeutic interventions. In this study, Medicarpin (Med), a natural pterocarpan, was selected (by screening) as a small-molecule inducer of adipocyte differentiation among 854 candidates by using C3H10T1/2 mesenchymal stem cell; a cellular model of adipogenesis. Med induced the expression of brown-adipocyte commitment marker Bmp7 as well as the early regulators of brown fat fate Pparγ, Prdm16, and Pgc-1α during differentiation of C3H10T1/2 mesenchymal stem cells...
October 24, 2017: BioFactors
https://www.readbyqxmd.com/read/29040444/re-establishment-of-energy-balance-in-a-male-mouse-model-with-pomc-neuron-deletion-of-bmpr1a
#6
Kristy L Townsend, Christopher Madden, Magdalena Blaszkiewicz, Lindsay McDougall, Domenico Tupone, Matthew D Lynes, Yuji Mishina, Paul Yu, Shaun Morrison, Yu-Hua Tseng
The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein 7 (BMP7) reduces appetite. Now we show that a type 1 BMP receptor, BMPR1A, is co-localized with POMC neurons and POMC-BMPR1A-KO mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibit a lack of obesity, even on a 45% high-fat diet...
October 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/29039494/internal-driving-factors-leading-to-extrahepatic-manifestation-of-the-hepatitis%C3%A2-c-virus-infection
#7
Zhou-Yi Wu, Jian-Rui Li, Meng-Hao Huang, Jun-Jun Cheng, Hu Li, Jin-Hua Chen, Xiao-Qin Lv, Zong-Gen Peng, Jian-Dong Jiang
The hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, which are correlated with poor outcomes, and thus increase the morbidity and mortality of chronic hepatitis C (CHC). Therefore, understanding the internal linkages between systemic manifestations and HCV infection is helpful for treatment of CHC. Yet, the mechanism by which the virus evokes the systemic diseases remains to be elucidated. In the present study, using gene set enrichment analysis (GSEA) and signaling pathway impact analysis (SPIA), a comprehensive analysis of microarray data of mRNAs was conducted in HCV-infected and -uninfected Huh7...
October 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28980745/leptin-differentially-regulates-endochondral-ossification-in-tibial-and-vertebral-epiphyseal-plates
#8
Xiaomiao Li, Sheng Shi, Jianwei Chen, Guibin Zhong, Xinfeng Li, Zude Liu
Longitudinal bone growth is governed by a complex network of endocrine signals including leptin. In mouse, leptin deficiency leads to distinct phenotypes in bones of the limb and spine, suggesting the appendicular and axial skeletons are subject to differential regulation by leptin. We established primary cultures for the chondrocytes from tibial and vertebral epiphyseal plates. Cellular proliferation and apoptosis were analyzed for the chondrocytes that had been treated with various concentrations of leptin...
October 5, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28969601/genome-wide-analysis-of-dna-methylation-profiles-on-sheep-ovaries-associated-with-prolificacy-using-whole-genome-bisulfite-sequencing
#9
Yanli Zhang, Fengzhe Li, Xu Feng, Hua Yang, Aoxiang Zhu, Jing Pang, Le Han, Tingting Zhang, Xiaolei Yao, Feng Wang
BACKGROUND: Ovulation rate and litter size are important reproductive traits in sheep with high economic value. Recent work has revealed a potential link between DNA methylation and prolificacy. However, a genome-wide study that sought to identify potential DNA methylation sites involved in sheep prolificacy indicated that it is still unknown. Here, we aimed to investigate the genome-wide DNA methylation profiles of Hu sheep ovaries by comparing a high-prolificacy group (HP, litter size of three for at least 2 consecutive lambings) and low prolificacy group (LP, litter size of one for at least 2 consecutive lambings) using deep whole-genome bisulfite sequencing (WGBS)...
October 2, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28925495/laminin-associated-with-bmp7-as-potential-secondary-astrocytic-glioma-fiber-differentiation-targets
#10
G-S Mao, M Yan, Z-Z Ma, L-Z Sun, Y Liu
OBJECTIVE: To investigate the activation of the BMP7 and laminin pathway is associated with glioma cell proliferation and differentiation. PATIENTS AND METHODS: We enrolled 65 patients with primary operable glioma. Laminin and BMP7 protein expression and its subcellular localization were studied by immunofluorescence. RESULTS: We detected a higher level of BMP7 expression in glioma tissue in patients with a lower grade of glioma who had a lower eosinophil count...
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28924042/alternative-cleavage-of-the-bone-morphogenetic-protein-bmp-gbb-produces-ligands-with-distinct-developmental-functions-and-receptor-preference
#11
Edward N Anderson, Kristi A Wharton
The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins have numerous developmental and physiological roles. They are made as proprotein dimers, then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer. Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms. Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, while NS site cleavage produces a larger Gbb38 ligand...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28923783/bmp7-induced-pten-inhibits-akt-and-prevents-renal-fibrosis
#12
Debra F Higgins, Leah M Ewart, Enda Masterson, Sadhbh Tennant, Gleb Grebnev, Marco Prunotto, Sylvia Pomposiello, Karin Conde-Knape, Finian M Martin, Catherine Godson
Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFβ1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFβ1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300μg/kg i.p.) every other day for eight days and kidneys analysed for markers of fibrosis and SMAD, MAPK, and PI3K signaling...
September 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28867673/bmp7-dose-dependently-stimulates-proliferation-and-cadherin-11-expression-via-erk-and-p38-in-a-murine-metanephric-mesenchymal-cell-line
#13
Midori Awazu, Michio Nagata, Mariko Hida
BMP7 is expressed in ureteric buds and cap mesenchyme of the fetal kidney, mediating branching morphogenesis and survival and priming of metanephric mesenchyme. Although dose-dependent effects of BMP7 in collecting duct cells have been reported, studies in metanephric mesenchymal cells are lacking. We examined the effects of BMP7 on MAP kinase activation, proliferation, and expression of cadherins in a metanephric mesenchymal cell line MS7 by thymidine incorporation, immunoblot analysis, and quantitative real-time PCR The levels of phosphorylated ERK (P-ERK) and phosphorylated p38 (P-p38) were not altered at 10 min, 1 h, and 6 h with low-dose BMP7 (0...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28862380/fetal-bone-marrow-derived-mesenchymal-stem-stromal-cells-enhance-humanization-and-bone-formation-of-bmp7-loaded-scaffolds
#14
Abbas Shafiee, Jeremy G Baldwin, Jatin Patel, Boris M Holzapfel, Nicholas M Fisk, Kiarash Khosrotehrani, Dietmar W Hutmacher
Tissue engineered constructs built with human cells capable of generating a bone-like organ within the mouse have attracted considerable interest over the past decade. Here, we aimed to compare the utility of human mesenchymal stem/stromal cells (MSC) isolated from fetal term placenta (fPL-MSC) and fetal first trimester bone marrow (fBM-MSC) in a polycaprolactone scaffold/BMP7-based model in nude mice. Furthermore, fPL-MSC were co-seeded with fetal placenta-derived endothelial colony forming cells (ECFC) to assess the impact of ECFC on fPL-MSC osteogenesis...
September 1, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28855249/lncrna-chronos-is-an-aging-induced-inhibitor-of-muscle-hypertrophy
#15
Ronald L Neppl, Chia-Ling Wu, Kenneth Walsh
Skeletal muscle exhibits remarkable plasticity in its ability to modulate its mass in response to the physiologic changes associated with functional use, systemic disease, and aging. Although a gradual loss of muscle mass normally occurs with advancing age, its increasingly rapid progression results in sarcopenia in a subset of individuals. The identities of muscle-enriched, long noncoding RNAs that regulate this process are unknown. Here, we identify a long noncoding RNA, named Chronos, whose expression in muscle is positively regulated with advancing age and negatively regulated during Akt1-mediated growth...
November 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28834244/striking-a-new-path-in-reducing-cartilage-breakdown-combination-of-antioxidative-therapy-and-chondroanabolic-stimulation-after-blunt-cartilage-trauma
#16
Jana Riegger, Helga Joos, Hans-Georg Palm, Benedikt Friemert, Heiko Reichel, Anita Ignatius, Rolf E Brenner
Cartilage injury can trigger crucial pathomechanisms, including excessive cell death and expression of matrix-destructive enzymes, which contribute to the progression of a post-traumatic osteoarthritis (PTOA). With the intent to create a novel treatment strategy for alleviating trauma-induced cartilage damage, we complemented a promising antioxidative approach based on cell and chondroprotective N-acetyl cysteine (NAC) by chondroanabolic stimulation. Overall, three potential pro-anabolic growth factors - IGF-1, BMP7 and FGF18 - were tested comparatively with and without NAC in an ex vivo human cartilage trauma-model...
August 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28815607/a-3d-tri-culture-system-reveals-that-activin-receptor-like-kinase-5-and-connective-tissue-growth-factor-drive-human-glomerulosclerosis
#17
John P Waters, Yvonne C Richards, Jeremy N Skepper, Mark Southwood, Paul D Upton, Nicholas W Morrell, Jordan S Pober, John R Bradley
Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GECs), podocytes, and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis...
November 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28814567/cbf%C3%AE-2-deficiency-preserves-langerhans-cell-precursors-by-lack-of-selective-tgf%C3%AE-receptor-signaling
#18
Mari Tenno, Katsuyuki Shiroguchi, Sawako Muroi, Eiryo Kawakami, Keita Koseki, Kirill Kryukov, Tadashi Imanishi, Florent Ginhoux, Ichiro Taniuchi
The mouse Langerhans cell (LC) network is established through the differentiation of embryonic LC precursors. BMP7 and TGFβ1 initiate cellular signaling that is essential for inducing LC differentiation and preserving LCs in a quiescent state, respectively. Here we show that loss of Cbfβ2, one of two RNA splice variants of the Cbfb gene, results in long-term persistence of embryonic LC precursors after their developmental arrest at the transition into the EpCAM(+) stage. This phenotype is caused by selective loss of BMP7-mediated signaling essential for LC differentiation, whereas TGFβR signaling is intact, maintaining cells in a quiescent state...
October 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28812969/functional-expression-of-bmp7-receptors-in-oral-epithelial-cells-interleukin-17f-production-in-response-to-bmp7
#19
Kensuke Nishio, Yasumasa Ozawa, Hisanori Ito, Takashi Kifune, Tatsuya Narita, Toshimitsu Iinuma, Nobuhito Gionhaku, Masatake Asano
BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily. Recently, BMP7 has been demonstrated to be produced by salivary glands and contribute to embryonic branching in mice. The BMP7 in saliva is thought to be delivered to the oral cavity and is expected to contact with stratified squamous epithelial cells which line the surface of oral mucosa. In this study, we attempted to investigate the effects of BMP7 on oral epithelial cells...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28807877/cryptotanshinone-promotes-commitment-to-the-brown-adipocyte-lineage-and-mitochondrial-biogenesis-in-c3h10t1-2-mesenchymal-stem-cells-via-ampk-and-p38-mapk-signaling
#20
Khan Mohammad Imran, Naimur Rahman, Dahyeon Yoon, Miso Jeon, Byong-Taek Lee, Yong-Sik Kim
Although white adipose tissue (WAT) stores triglycerides and contributes to obesity, brown adipose tissue (BAT) dissipates energy as heat. Therefore, browning of WAT is regarded as an attractive way to counteract obesity. Our previous studies have revealed that treatment with cryptotanshinone (CT) during adipogenesis of 3T3-L1 cells inhibits their differentiation. Here, we found that pretreatment of C3H10T1/2 mesenchymal stem cells with CT before exposure to adipogenic hormonal stimuli promotes the commitment of these mesenchymal stem cells to the adipocyte lineage as confirmed by increased triglyceride accumulation...
October 2017: Biochimica et Biophysica Acta
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