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https://www.readbyqxmd.com/read/28815688/bmp2-controls-iron-homeostasis-in-mice-independent-of-bmp6
#1
Susanna Canali, Chia-Yu Wang, Kimberly B Zumbrennen-Bullough, Abraham Bayer, Jodie L Babitt
Hepcidin is a key iron regulatory hormone that controls expression of the iron exporter ferroportin to increase the iron supply when needed to support erythropoiesis and other essential functions, but to prevent the toxicity of iron excess. The bone morphogenetic protein (BMP)-SMAD signaling pathway, through the ligand BMP6 and the co-receptor hemojuvelin, is a central regulator of hepcidin transcription in the liver in response to iron. Here, we show that dietary iron loading has a residual ability to induce Smad signaling and hepcidin expression in Bmp6-/- mice, effects that are blocked by a neutralizing BMP2/4 antibody...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28814721/acceleration-of-osteoblast-differentiation-by-a-novel-osteogenic-compound-dmp-pyt-through-activation-of-both-the-bmp-and-wnt-pathways
#2
Su Jung Bae, Hye Joo Kim, Hee Yeon Won, Yong Ki Min, Eun Sook Hwang
Osteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/β-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and β-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814648/zc4h2-stabilizes-smads-to-enhance-bmp-signalling-which-is-involved-in-neural-development-in-xenopus
#3
Pengcheng Ma, Biyu Ren, Xiangcai Yang, Bin Sun, Xiaoliang Liu, Qinghua Kong, Chaocui Li, Bingyu Mao
Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance, differentiation and embryonic development. Intracellularly, BMP signalling is mediated by Smad proteins, which are regulated post-transcriptionally through reversible phosphorylation and ubiquitination. ZC4H2 is a small nuclear protein associated with intellectual disability and neural development in humans. Here, we report that ZC4H2 is highly expressed in the developing neural system and is involved in neural patterning and BMP signalling in Xenopus Knockdown of ZC4H2 led to expansion of the expression of the pan neural plate marker Sox2 in Xenopus embryos...
August 2017: Open Biology
https://www.readbyqxmd.com/read/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#4
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28765970/bmp-7-enhances-snon-mrna-expression-in-renal-tubular-epithelial-cells-under-high-glucose-conditions
#5
Yuanyuan Wang, Ying Xiao, Shuang Li, Lei Shi, Lirong Liu, Yingying Zhang, Mingjun Shi, Bing Guo
The present study aimed to identify any association between bone morphogenetic protein‑7 (BMP‑7) and the expression of the transcriptional co‑repressor Ski‑related novel protein N (SnoN), in addition to alterations in tubulointerstitial fibrosis, during the development and progression of diabetic nephropathy (DN). Streptozotocin was injected into the tail veins of 20 healthy and specific pathogen‑free male Sprague‑Dawley rats. The rats were sacrificed to detect the appropriate biochemical indicators of renal pathological alterations following 24 weeks...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28760815/endothelial-cells-respond-to-the-direction-of-mechanical-stimuli-through-smad-signaling-to-regulate-coronary-artery-size
#6
Aruna Poduri, Brian Raftrey, Andrew H Chang, Siyeon Rhee, Mike Van, Kristy Red-Horse
How mechanotransduction intersects with chemical and transcriptional factors to shape organogenesis is an important question in developmental biology. This is particularly relevant to the cardiovascular system, which uses mechanical signals from flowing blood to stimulate cytoskeletal and transcriptional responses that form a highly efficient vascular network. Using this system, artery size and structure are tightly regulated, but the underlying mechanisms are poorly understood. Here, we demonstrate that deletion of Smad4 increased the diameter of coronary arteries during embryonic development, a phenotype that followed the initiation of blood flow...
July 31, 2017: Development
https://www.readbyqxmd.com/read/28736908/bmp-7-ameliorates-cobalt-alloy-particle-induced-inflammation-by-suppressing-th17-responses
#7
Fengrong Chen, Ruisong Chen, Haoyuan Liu, Rupeng Sun, Jianming Huang, Zheyuan Huang, Guojian Jian
Metal wear debris has been shown to activate an aseptic osteolytic process that causes failure in total joint arthroplasty (TJA). This osteolysis is characterized by a proinflammatory, self-propagating immune response involving primarily macrophages, dendritic cells, and activated osteoclasts, as well as T cells and B cells. The human bone morphogenic protein (BMP)-7, on the other hand, was shown to promote osteoblast survival, and reversed the downregulation of anabolic Smad proteins and Runx2 following cobalt injury...
July 24, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28725489/bmp-2-induces-emt-and-breast-cancer-stemness-through-rb-and-cd44
#8
Peide Huang, Anan Chen, Weiyi He, Zhen Li, Guanglin Zhang, Zhong Liu, Ge Liu, Xueting Liu, Shuilian He, Gang Xiao, Feicheng Huang, Jan Stenvang, Nils Brünner, An Hong, Ju Wang
Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms underlying its influence on breast cancer metastasis, we conducted a comprehensive molecular study using breast cancer cell lines and clinical samples. Our results showed that downregulation of Rb by BMP-2 was associated with ubiquitin-mediated degradation activated by phosphorylation of Rb via the PI3K/AKT signal pathway...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28718708/enhanced-bone-repair-induced-by-human-adipose-derived-stem-cells-on-osteogenic-extracellular-matrix-ornamented-small-intestinal-submucosa
#9
Chi Zhang, Mei Li, Jinjin Zhu, Fangmiao Luo, Jiyuan Zhao
AIM: Our aim was to design an osteogenic extracellular matrix (ECM) coated bioscaffold and to apply it to critical bone defect repair with adipose-derived stem cells (ADSCs). MATERIALS & METHODS: Morphology of scaffolds was scanned by scanning electron microscope. Cell adhesion, proliferation and osteogenic differentiation of ADSCs on ECM-small intestinal submucosa (SIS) were evaluated by immunofluorescences staining, cell counting kit-8 and real-time qPCR, respectively...
July 18, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28704388/the-mir-23a-27a-24-2-microrna-cluster-buffers-transcription-and-signaling-pathways-during-hematopoiesis
#10
Jeffrey L Kurkewich, Justin Hansen, Nathan Klopfenstein, Helen Zhang, Christian Wood, Austin Boucher, Joseph Hickman, David E Muench, H Leighton Grimes, Richard Dahl
MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28703293/bmp-and-tgf%C3%AE-signaling-regulate-the-formation-of-m%C3%A3-ller-glia-derived-progenitor-cells-in-the-avian-retina
#11
Levi Todd, Isabella Palazzo, Natalie Squires, Ninoshka Mendonca, Andy J Fischer
Müller glia-derived progenitor cells (MGPCs) have the capability to regenerate neurons in the retinas of different vertebrate orders. The formation of MGPCs is regulated by a network of cell-signaling pathways. The purpose of this study was to investigate how BMP/Smad1/5/8- and TGFβ/Smad2/3-signaling are coordinated to influence the formation of MGPCs in the chick model system. We find that pSmad1/5/8 is selectively up-regulated in the nuclei of Müller glia following treatment with BMP4, FGF2, or NMDA-induced damage, and this up-regulation is blocked by a dorsomorphin analogue DMH1...
July 13, 2017: Glia
https://www.readbyqxmd.com/read/28697500/cx43-and-smad-mediated-tgf-%C3%AE-bmp-signaling-pathway-promotes-cartilage-differentiation-of-bone-marrow-mesenchymal-stem-cells-and-inhibits-osteoblast-differentiation
#12
Ya-Dong Zhang, Shi-Chang Zhao, Zhong-Sheng Zhu, Yi-Fei Wang, Jian-Xiang Liu, Zhi-Cai Zhang, Feng Xue
BACKGROUND/AIMS: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-β/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. METHODS: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28688217/yes-associated-protein-1-promotes-the-differentiation-and-mineralization-of-cementoblast
#13
Beining Yang, Hualing Sun, Fangfang Song, Yanru Wu, Jiawei Wang
Yes-associated protein 1 (YAP1) transcriptional coactivator is a mediator of mechanosensitive signaling. Cementum, which covers the tooth root surface, continuously senses external mechanical stimulation. Cementoblasts are responsible for the mineralization and maturation of the cementum. However, the effect of YAP1 on cementoblast differentiation remains largely unknown. In this study, we initially demonstrated that YAP1 overexpression enhanced the mineralization ability of cementoblasts. YAP1 upregulated the mRNA and protein expression of several cementogenesis markers, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and dentin matrix acidic phosphoprotein 1 (DMP1)...
July 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28684382/a-regulatory-role-of-androgen-in-ovarian-steroidogenesis-by-rat-granulosa-cells
#14
Toru Hasegawa, Yasuhiko Kamada, Takeshi Hosoya, Shiho Fujita, Yuki Nishiyama, Nahoko Iwata, Yuji Hiramatsu, Fumio Otsuka
Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells...
September 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28680581/endothelial-follistatin-like-1-regulates-the-postnatal-development-of-the-pulmonary-vasculature-by-modulating-bmp-smad-signaling
#15
Navessa P Tania, Harm Maarsingh, I Sophie T Bos, Andrea Mattiotti, Stuti Prakash, Wim Timens, Quinn D Gunst, Luis J Jimenez-Borreguero, Martina Schmidt, Maurice J B van den Hoff, Reinoud Gosens
Bone morphogenetic protein (BMP) signaling regulates vascular smooth muscle maturation, endothelial cell proliferation, and tube formation. The endogenous BMP antagonist Follistatin-like 1 (Fstl1) is highly expressed in pulmonary vascular endothelium of the developing mouse lung, suggesting a role in pulmonary vascular formation and vascular homeostasis. The aim of this study was to investigate the role of Fstl1 in the pulmonary vascular endothelium. To this aim, Fstl1 was conditionally deleted from endothelial and endothelial-derived cells using Tie2-cre driven Fstl1-KO mice (Fstl1-eKO mice)...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28680159/peptides-derived-from-the-knuckle-epitope-of-bmp-9-induce-the-cholinergic-differentiation-and-inactivate-gsk3beta-in-human-sh-sy5y-neuroblastoma-cells
#16
Marc-Antoine Lauzon, Olivier Drevelle, Nathalie Faucheux
The incidence of brain degenerative disorders like Alzheimer's disease (AD) will increase as the world population ages. While there is presently no known cure for AD and current treatments having only a transient effect, an increasing number of publications indicate that growth factors (GF) may be used to treat AD. GFs like the bone morphogenetic proteins (BMPs), especially BMP-9, affect many aspects of AD. However, BMP-9 is a big protein that cannot readily cross the blood-brain barrier. We have therefore studied the effects of two small peptides derived from BMP-9 (pBMP-9 and SpBMP-9)...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28656211/notch-signaling-pathway-promotes-osteogenic-differentiation-of-mesenchymal-stem-cells-by-enhancing-bmp9-smad-signaling
#17
Junjie Cao, Yalin Wei, Jing Lian, Lunyun Yang, Xiaoyan Zhang, Jiaying Xie, Qiang Liu, Jinyong Luo, Baicheng He, Min Tang
Notch is an important pathway in that it regulates cell-to-cell signal transduction, which plays an essential role in skeletal remodeling. Bone morphogenetic protein (BMP)9 has been regarded as one of the most efficient BMPs by which to induce osteogenic differentiation in mesenchymal stem cells (MSCs). Understanding the interaction between Notch and BMP9 signaling is a critical issue for optimizing the application of MSCs and BMPs in bone tissue engineering. In the present study, we investigated the role of Notch signaling in the BMP9‑induced osteogenic differentiation of MSCs...
June 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28646109/bone-morphogenetic-protein-bmp-9-and-bmp10-enhance-tumor-necrosis-factor-%C3%AE-induced-monocyte-recruitment-to-the-vascular-endothelium-mainly-via-activin-receptor-like-kinase-2
#18
Claudia-Gabriela Mitrofan, Sarah L Appleby, Gerard B Nash, Ziad Mallat, Edwin R Chilvers, Paul D Upton, Nicholas W Morrell
Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an in vitro flow adhesion assay. Herein, we report that while BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergised with Tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with upregulated expression levels of E-selectin, VCAM-1 and ICAM-1 on endothelial cells...
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28642261/transforming-growth-factor-beta-stimulates-smad1-5-signaling-in-pulmonary-artery-smooth-muscle-cells-and-fibroblasts-of-the-newborn-mouse-through-alk1
#19
Huili Zhang, Lili Du, Ying Zhong, Kathleen C Flanders, Jesse D Roberts
The intracellular signaling mechanisms through which TGFβ regulates pulmonary development are incompletely understood. Canonical TGFβ signaling involves Smad2/3 phosphorylation, Smad2/3·Smad4 complex formation and nuclear localization, and gene regulation. Here we show that physiologically relevant TGFβ1 levels also stimulate Smad1/5 phosphorylation, typically a mediator of bone morphogenetic protein (BMP) signaling, in mouse pup pulmonary artery smooth muscle cells (mPASMC) and lung fibroblasts and other interstitial lung cell lines...
June 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28641928/bmpr1a-is-a-major-type-1-bmp-receptor-for-bmp-smad-signaling-during-skull-development
#20
Haichun Pan, Honghao Zhang, Ponnu Abraham, Yoshihiro Komatsu, Karen Lyons, Vesa Kaartinen, Yuji Mishina
Craniosynostosis is caused by premature fusion of one or more sutures in an infant skull, resulting in abnormal facial features. The molecular and cellular mechanisms by which genetic mutations cause craniosynostosis are incompletely characterized, and many of the causative genes for diverse types of syndromic craniosynostosis have not yet been identified. We previously demonstrated that augmentation of BMP signaling mediated by a constitutively active BMP type IA receptor (ca-BmpR1A) in neural crest cells (ca1A hereafter) causes craniosynostosis and superimposition of heterozygous null mutation of Bmpr1a rescues premature suture fusion (ca1A;1aH hereafter)...
September 1, 2017: Developmental Biology
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