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BMP AND smad

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https://www.readbyqxmd.com/read/28059064/bmp-restricts-stemness-of-intestinal-lgr5-stem-cells-by-directly-suppressing-their-signature-genes
#1
Zhen Qi, Yehua Li, Bing Zhao, Chi Xu, Yuan Liu, Haonan Li, Bingjie Zhang, Xinquan Wang, Xiao Yang, Wei Xie, Baojie Li, Jing-Dong Jackie Han, Ye-Guang Chen
The intestinal epithelium possesses a remarkable self-renewal ability, which is mediated by actively proliferating Lgr5(+) stem cells. Bone morphogenetic protein (BMP) signalling represents one major counterforce that limits the hyperproliferation of intestinal epithelium, but the exact mechanism remains elusive. Here we demonstrate that epithelial BMP signalling plays an indispensable role in restricting Lgr5(+) stem cell expansion to maintain intestinal homeostasis and prevent premalignant hyperproliferation on damage...
January 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28040510/du-huo-ji-sheng-tang-and-its-active-component-ligusticum-chuanxiong-promote-osteogenic-differentiation-and-decrease-the-aging-process-of-human-mesenchymal-stem-cells
#2
Jir-You Wang, Che-Sheng Wen, Shih-Chieh Hung, Pei-Wen Chen, Jen-Hwey Chiu
ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis is the most common bone disease worldwide. Information concerning the effects of herbal medicines on mesenchymal cell osteogenesis and senescence remains lacking. AIM OF THIS STUDY: This study was designed to investigate the effects of Du-Huo-Ji-Sheng-Tang (DHJST), a Chinese herbal medicine and its active component Ligusticum chuanxiong on osteogenic differentiation and the aging process of human mesenchymal cells (hMSCs)...
December 28, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28030800/the-role-of-mir-17-92-in-the-miregulatory-landscape-of-ewing-sarcoma
#3
Raphaela Schwentner, David Herrero-Martin, Maximilian O Kauer, Cornelia N Mutz, Anna M Katschnig, Grzegorz Sienski, Javier Alonso, Dave Nt Aryee, Heinrich Kovar
MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3'UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing sarcoma. MiR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be among the top EWS-FLI1 activated miRNAs...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029182/nedd4-deficiency-in-vascular-smooth-muscle-promotes-vascular-calcification-by-stabilizing-psmad1
#4
Ji-Hyun Lee, Seon-Ae Jeon, Byung-Gyu Kim, Michiko Takeda, Jae-Jin Cho, Dong-Ik Kim, Hiroshi Kawabe, Je-Yoel Cho
The nonosseous calcification process such as atherosclerosis is one of the major complications in several types of metabolic diseases. In previous study, we uncovered that aberrant activity of TGF-β signaling pathway could contribute the vascular smooth muscle cells (VSMCs) calcification process. Also, we identified NEDD4 E3 ligase as a key suppressor of BMP/Smad pathway via a polyubiquitination dependent selective degradation of C-terminal phosphorylated Smad1 (pSmad1) activated by TGF-β⋅ Here, we further validated and confirmed the role of Nedd4 in in vivo vascular calcification progression...
December 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27996168/follicle-stimulating-hormone-%C3%AE-subunit-potentiates-bone-morphogenetic-protein-9-induced-osteogenic-differentiation-in-mouse-embryonic-fibroblasts
#5
Xiao-Ya Su, Xiang Zou, Qian-Zhao Chen, Yu-Hua Zeng, Ying Shao, Bai-Cheng He, Hong Liu
Postmenopausal osteoporosis (PMOP)-related fractures usually result in morbidity and mortality in aging women, so it is remains a global public health concern, and new effective safe treatments are urgently needed recently. Efficient osteogenesis from mesenchymal stem cells (MSCs) would have the clinical application potential in treating multiple osteal disorders. Follicle-stimulating hormone (FSH), a pituitary glycoprotein hormone highly associated with menopausal bone turnover, whose peculiar part of receptor binding is follicle-stimulating hormone β-subunit (FSHβ)...
December 20, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27995357/bone-morphogenetic-protein-modulator-bmper-regulates-endothelial-barrier-function
#6
Thomas Helbing, Gwendoline Wiltgen, Alexandra Hornstein, Elena Z Brauers, Linus Arnold, Adrian Bauer, Jennifer S Esser, Philipp Diehl, Sebastian Grundmann, Katrin Fink, Cam Patterson, Christoph Bode, Martin Moser
The endothelium serves as a selective barrier and controls the exchange of nutrients, hormones, and leukocytes between blood and tissues. Molecular mechanisms contributing to the pathogenesis of endothelial barrier dysfunction remain incompletely understood. Accumulating evidence implicates bone morphogenetic protein (BMP)-modulator BMPER as a key regulator in endothelial biology. Herein, we analyze the impact of BMPER in the control of endothelial barrier function. To assess the role of BMPER in vascular barrier function in mice, we measured the leakage of Evans blue dye from blood into interstitial lung tissue...
December 19, 2016: Inflammation
https://www.readbyqxmd.com/read/27986931/bone-morphogenetic-protein-2-regulates-cell-cell-communication-by-down-regulating-connexin43-expression-in-luteinized-human-granulosa-cells
#7
Yan-Ting Wu, Hsun-Ming Chang, He-Feng Huang, Jian-Zhong Sheng, Peter C K Leung
STUDY QUESTION: Does bone morphogenetic protein 2 (BMP2) regulate connexin43 (Cx43) and modulate cell-cell communication in luteinized human granulosa cells? SUMMARY ANSWER: BMP2 decreases gap junction intercellular communication (GJIC) of luteinized human granulosa cells by down-regulating Cx43 expression through an activin receptor-like kinase (ALK)2/ALK3-mediated Sma- and Mad-related protein (SMAD)-dependent signaling pathway. WHAT IS KNOWN ALREADY: BMP2 and its putative receptors are highly expressed in the human corpus luteum and are involved in the process of luteolysis...
December 16, 2016: Molecular Human Reproduction
https://www.readbyqxmd.com/read/27979781/the-binding-of-the-bone-morphogenetic-protein-antagonist-gremlin-to-kidney-heparan-sulfate-such-binding-is-not-essential-for-bmp-antagonism
#8
Arnold Junior Tatsinkam, Naomi Rune, Joy Smith, Jill T Norman, Barbara Mulloy, Christopher C Rider
Gremlin-1, a bone morphogenetic protein (BMP) antagonist, has essential roles in kidney and limb bone development, and is important in chronic diseases including tissue fibrosis. It also functions as an activating ligand of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), and binds strongly to the sulfated polysaccharide, heparin. Here we investigated the extent to which gremlin binds to the related polysaccharide heparan sulfate (HS), which unlike heparin is widely distributed spread within tissues...
December 12, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27941807/self-organized-amniogenesis-by-human-pluripotent-stem-cells-in-a-biomimetic-implantation-like-niche
#9
Yue Shao, Kenichiro Taniguchi, Katherine Gurdziel, Ryan F Townshend, Xufeng Xue, Koh Meng Aw Yong, Jianming Sang, Jason R Spence, Deborah L Gumucio, Jianping Fu
Amniogenesis-the development of amnion-is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment...
December 12, 2016: Nature Materials
https://www.readbyqxmd.com/read/27932702/incorporation-of-cerium-oxide-into-hydroxyapatite-coating-regulates-osteogenic-activity-of-mesenchymal-stem-cell-and-macrophage-polarization
#10
Kai Li, Qingyi Shen, Youtao Xie, Mingyu You, Liping Huang, Xuebin Zheng
Biomedical coatings for orthopedic implants should facilitate osseointegration and mitigate implant-induced inflammatory reactions. Cerium oxide (CeO2) ceramics possess anti-oxidative properties and can be used to decrease mediators of inflammation, which makes them attractive for biomedical applications. In our work, two kinds of CeO2 incorporated hydroxyapatite coatings (HA-10Ce and HA-30Ce) were prepared via plasma spraying technique and the effects of CeO2 addition on the responses of bone mesenchymal stem cells (BMSCs) and RAW264...
December 8, 2016: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/27922109/regulation-of-hepcidin-expression-by-inflammation-induced-activin-b
#11
Yohei Kanamori, Makoto Sugiyama, Osamu Hashimoto, Masaru Murakami, Tohru Matsui, Masayuki Funaba
Activin B is induced in response to inflammation in the liver and enhances hepcidin expression, but the source of activin B and the molecular mechanism underlying hepcidin induction are not clear yet. Lipopolysaccharide (LPS)-induced inflammation induced inhibin βB but not inhibin α or inhibin βA expression in the liver, implicating activin B induction. Immunoreactive inhibin βB was detected in endothelial cells and Kupffer cells in LPS-treated liver. Activin B, but not activin A or activin AB, directly increased hepcidin expression...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920040/regulation-of-tgf-%C3%AE-family-signaling-by-inhibitory-smads
#12
Keiji Miyazawa, Kohei Miyazono
Inhibitory Smads (I-Smads) have conserved carboxy-terminal MH2 domains but highly divergent amino-terminal regions when compared with receptor-regulated Smads (R-Smads) and common-partner Smads (co-Smads). Smad6 preferentially inhibits Smad signaling initiated by the bone morphogenetic protein (BMP) type I receptors ALK-3 and ALK-6, whereas Smad7 inhibits both transforming growth factor β (TGF-β)- and BMP-induced Smad signaling. I-Smads also regulate some non-Smad signaling pathways. Here, we discuss the vertebrate I-Smads, their roles as inhibitors of Smad activation and regulators of receptor stability, as scaffolds for non-Smad signaling, and their possible roles in the nucleus...
December 5, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27911728/modulation-of-bmp-signalling-by-integrins
#13
REVIEW
Hilary L Ashe
The bone morphogenetic protein (BMP) pathway is a major conserved signalling pathway with diverse roles in development and homeostasis. Given that cells exist in three-dimensional environments, one important area is to understand how the BMP pathway operates within such complex cellular environments. The extracellular matrix contains information regarding tissue architecture and its mechanical properties that is transmitted to the cell via integrin receptors. In this review, I describe various examples of modulation of the BMP pathway by integrins...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27909410/mechanosensitive-molecular-networks-involved-in-transducing-resistance-exercise-signals-into-muscle-protein-accretion
#14
REVIEW
Emil Rindom, Kristian Vissing
Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27905054/crosstalk-between-shh-and-stemness-state-signaling-pathways-in-esophageal-squamous-cell-carcinoma
#15
Maryam Najafi, Mohammad Reza Abbaszadegan, Abolfazl Rad, Mahtab Dastpak, Samaneh Boroumand-Noughabi, Mohammad Mahdi Forghanifard
The expression of GLI1 as a downstream gene of sonic hedgehog (Hh) pathway, studied in a variety of cancers including esophageal squamous cell carcinoma (ESCC). However, the interaction of Hh with other developmental pathways needs to be elucidated. In this study, we aimed to investigate the correlation of GLI1 expression with transcription factors (TFs) of stem cell signaling pathways, and their association with clinico-pathological data of ESCC. Using real-time PCR, we assessed the expression of GLI1 mRNA in 49 ESCC patients, and analyzed the correlation between GLI1 and selected TFs...
November 30, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27890611/histone-methyltransferase-setdb1-is-indispensable-for-meckel-s-cartilage-development
#16
Kohei Yahiro, Norihisa Higashihori, Keiji Moriyama
The histone methyltransferase Setdb1 represses gene expression by catalyzing lysine 9 of histone H3 trimethylation. Given that the conventional knockout of Setdb1 is embryo-lethal at the implantation stage, its role in craniofacial development is poorly understood. Here, we investigated the role of Setdb1, using conditional knockout mice-in which Setdb1 was deleted in the Meckel's cartilage (Setdb1 CKO)-and the mouse chondrogenic cell line ATDC5-in which Setdb1 was inhibited by siRNA. Deletion of Setdb1 in Meckel's cartilage, the supportive tissue in the embryonic mandible, led to its enlargement, instead of the degeneration that normally occurs...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27856249/the-transcriptional-modulator-ifrd1-is-a-negative-regulator-of-bmp-2-dependent-osteoblastogenesis
#17
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...
January 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27844469/the-expression-of-smad-signaling-pathway-in-myocardium-and-potential-therapeutic-effects
#18
REVIEW
Yuping Duan, Wei Zhu, Min Liu, Muhammad Ashraf, Meifeng Xu
Myocardial infarction (MI) is a life-threatening disease. The expression of Smad proteins in the ischemic myocardium changes significantly following myocardial infarction, suggesting a close relationship between Smad proteins and heart remodeling. Moreover, it is known that the expression of Smads is regulated by transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMP). Based on these findings, regulating the expression of Smad proteins by targeting TGF-β and BMP in the ischemic myocardium may be considered to be a possible therapeutic strategy for the treatment of myocardial infarction...
November 15, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27836834/signaling-cross-talk-between-tgf-%C3%AE-smad-and-other-signaling-pathways
#19
REVIEW
Kunxin Luo
Cytokines of the transforming growth factor β (TGF-β) family, including TGF-βs, bone morphogenic proteins (BMPs), activins, and Nodal, play crucial roles in embryonic development and adult tissue homeostasis by regulating cell proliferation, survival, and differentiation, as well as stem-cell self-renewal and lineage-specific differentiation. Smad proteins are critical downstream mediators of these signaling activities. In addition to regulating the transcription of direct target genes of TGF-β, BMP, activin, or Nodal, Smad proteins also participate in extensive cross talk with other signaling pathways, often in a cell-type- or developmental stage-specific manner...
January 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27834400/notch-regulates-bmp-responsiveness-and-lateral-branching-in-vessel-networks-via-smad6
#20
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
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