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BMP9

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https://www.readbyqxmd.com/read/29642505/bmp9-promotes-the-proliferation-and-migration-of-bladder-cancer-cells-through-up-regulating-lncrna-uca1
#1
Liyao Gou, Mengyao Liu, Jing Xia, Qun Wan, Yayun Jiang, Shilei Sun, Min Tang, Lan Zhou, Tongchuan He, Yan Zhang
As the most common malignant tumor of the urinary system worldwide, the bladder tumor has a high mortality rate, which is mainly due to its onset of concealment. Therefore, research into novel diagnostic markers and treatment of bladder cancer is urgently needed. BMP9 (Bone morphogenetic protein 9) is a member of BMP, which belongs to the TGF-β (transforming growth factor-β) superfamily. It has been associated with multiple tumors. We found that BMP9 is highly expressed in bladder cancer cells and it could significantly promote the proliferation and migration of bladder cancer cells...
April 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29542728/heart-failure-bmp9-is-an-inhibitor-of-cardiac-fibrosis
#2
Alexandra Le Bras
No abstract text is available yet for this article.
March 15, 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29512689/microrna-155-inhibits-the-osteogenic-differentiation-of-mesenchymal-stem-cells-induced-by-bmp9-via-downregulation-of-bmp-signaling-pathway
#3
Hongxia Liu, Liang Zhong, Taixian Yuan, Sicheng Chen, Yiqing Zhou, Liqin An, Yangliu Guo, Mengtian Fan, Ya Li, Yanting Sun, Wang Li, Qiong Shi, Yaguang Weng
Previous studies have indicated that bone morphogenetic protein 9 (BMP9) can promote the osteogenic differentiation of mesenchymal stem cells (MSCs) and increase bone formation in bone diseases. However, the mechanisms involved remained poorly understood. It is necessary to investigate the specific regulatory mechanisms of osteogenic differentiation that were induced by BMP9. During the process of osteogenic differentiation induced by BMP9, the expression of microRNA-155 (miR-155) exhibited a tendency of increasing at first and then decreasing, which made us consider that miR-155 may have a modulatory role in this process, but the roles of this process have not been elucidated...
March 1, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29500191/primary-cilia-sensitize-endothelial-cells-to-bmp-and-prevent-excessive-vascular-regression
#4
Anne-Clémence Vion, Silvanus Alt, Alexandra Klaus-Bergmann, Anna Szymborska, Tuyu Zheng, Tijana Perovic, Adel Hammoutene, Marta Bastos Oliveira, Eireen Bartels-Klein, Irene Hollfinger, Pierre-Emmanuel Rautou, Miguel O Bernabeu, Holger Gerhardt
Blood flow shapes vascular networks by orchestrating endothelial cell behavior and function. How endothelial cells read and interpret flow-derived signals is poorly understood. Here, we show that endothelial cells in the developing mouse retina form and use luminal primary cilia to stabilize vessel connections selectively in parts of the remodeling vascular plexus experiencing low and intermediate shear stress. Inducible genetic deletion of the essential cilia component intraflagellar transport protein 88 (IFT88) in endothelial cells caused premature and random vessel regression without affecting proliferation, cell cycle progression, or apoptosis...
March 2, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29487140/bone-morphogenetic-protein-9-reduces-cardiac-fibrosis-and-improves-cardiac-function-in-heart-failure
#5
Kevin J Morine, Xiaoying Qiao, Sam York, Peter S Natov, Vikram Paruchuri, Yali Zhang, Mark J Aronovitz, Richard H Karas, Navin K Kapur
Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity...
February 27, 2018: Circulation
https://www.readbyqxmd.com/read/29478089/serum-glucocorticoid-regulated-kinase-1-as-a-novel-transcriptional-target-of-bone-morphogenetic-protein-alk1-receptor-signaling-in-vascular-endothelial-cells
#6
Mutsumi Araki, Takashi Hisamitsu, Yumi Kinugasa-Katayama, Toru Tanaka, Yukihiro Harada, Shu Nakao, Sanshiro Hanada, Shuhei Ishii, Masahide Fujita, Teruhisa Kawamura, Yoshihiko Saito, Koichi Nishiyama, Yusuke Watanabe, Osamu Nakagawa
Bone morphogenetic protein 9 (BMP9)/BMP10-ALK1 receptor signaling is essential for endothelial differentiation and vascular morphogenesis. Mutations in ALK1/ACVRL1 and other signal-related genes are implicated in human vascular diseases, and the Alk1/Acvrl1 deletion in mice causes severe impairment of vascular formation and embryonic lethality. In the microarray screen to search for novel downstream genes of ALK1 signaling, we found that the mRNA and protein expression of serum/glucocorticoid-regulated kinase 1 (SGK1) was rapidly up-regulated by the BMP9 stimulation of cultured human endothelial cells...
February 24, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29449337/alk1-activin-receptor-like-kinase-1-loss-results-in-vascular-hyperplasia-in-mice-and-humans-through-pi3k-phosphatidylinositol-3-kinase-activation
#7
Elisenda Alsina-Sanchís, Yaiza García-Ibáñez, Ana M Figueiredo, Carla Riera-Domingo, Agnès Figueras, Xavier Matias-Guiu, Oriol Casanovas, Luisa M Botella, Miquel A Pujana, Antoni Riera-Mestre, Mariona Graupera, Francesc Viñals
OBJECTIVE: ALK1 (activin-receptor like kinase 1) is an endothelial cell-restricted receptor with high affinity for BMP (bone morphogenetic protein) 9 TGF-β (transforming growth factor-β) family member. Loss-of-function mutations in ALK1 cause a subtype of hereditary hemorrhagic telangiectasia-a rare disease characterized by vasculature malformations. Therapeutic strategies are aimed at reducing potential complications because of vascular malformations, but currently, there is no curative treatment for hereditary hemorrhagic telangiectasia...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29441951/lncrna-hulc-promotes-epithelial-and-smooth-muscle-like-differentiation-of-adipose-derived-stem-cells-by-upregulation-of-bmp9
#8
Yongwei Li, Zhengfei Shan, Bin Yang, Diandong Yang, Changping Men, Yuanshan Cui, Jitao Wu
AIMS: Adipose-derived stem cells (ADSCs), a source of mesenchymal stem cells, are able to differentiate into numerous cell lineages, including epithelial and smooth muscle cells. The use of ADSCs in tissue engineering technology has become the most promising therapeutic approach for urethral reconstruction. This study aimed to explore the effect of lncRNA highly upregulated in liver cancer (HULC) on the induction of ADSCs to differentiate into epithelial and smooth-muscle-like cells. METHODS: ADSCs were isolated from a male dog, and the expression of HULC in ADSCs was overexpressed by transfection with HULC expressing vector lentivirus...
January 2, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29429074/cyclic-mechanical-stretch-enhances-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells
#9
Yang Song, Yinhong Tang, Jinlin Song, Mingxing Lei, Panpan Liang, Tiwei Fu, Xudong Su, Pengfei Zhou, Li Yang, Enyi Huang
PURPOSE: The purpose of this study was to investigate whether mechanical stretch can enhance the bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation in MSCs. METHODS: Recombinant adenoviruses were used to overexpress the BMP9 in C3H10T1/2 MSCs. Cells were seeded onto six-well BioFlex collagen I-coated plates and subjected to cyclic mechanical stretch [6% elongation at 60 cycles/minute (1 Hz)] in a Flexercell FX-4000 strain unit for up to 12 hours...
February 10, 2018: International Orthopaedics
https://www.readbyqxmd.com/read/29377252/hmox1-promotes-osteogenic-differentiation-at-the-expense-of-reduced-adipogenic-differentiation-induced-by-bmp9-in-c3h10t1-2-cells
#10
Xiaohua Liu, Caixia Ji, Li Xu, TingTing Yu, Chaoqun Dong, Jinyong Luo
Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into a variety of cell types under proper stimuli. Bone morphogenetic protein 9 (BMP9) is able to simultaneously induce both adipogenic and osteogenic differentiation of MSCs although the regulatory molecules involved remain to be fully identified and characterized. Heme oxygenase 1 (Hmox1) plays an essential role not only in fat metabolism, but also in bone development. In the present study, we investigated the functional role of Hmox1 in BMP9-induced osteogenic/adipogenic differentiation in MSCs line C3H10T1/2 and probed the possible mechanism involved...
January 29, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29348202/molecular-characterization-of-latent-gdf8-reveals-mechanisms-of-activation
#11
Ryan G Walker, Jason C McCoy, Magdalena Czepnik, Melanie J Mills, Adam Hagg, Kelly L Walton, Thomas R Cotton, Marko Hyvönen, Richard T Lee, Paul Gregorevic, Craig A Harrison, Thomas B Thompson
Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-β. Using a combination of small-angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or "triggered" state where the prodomain remains in complex with the mature domain...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29340096/crispr-cas9-mediated-reversibly-immortalized-mouse-bone-marrow-stromal-stem-cells-bmscs-retain-multipotent-features-of-mesenchymal-stem-cells-mscs
#12
Xue Hu, Li Li, Xinyi Yu, Ruyi Zhang, Shujuan Yan, Zongyue Zeng, Yi Shu, Chen Zhao, Xingye Wu, Jiayan Lei, Yasha Li, Wenwen Zhang, Chao Yang, Ke Wu, Ying Wu, Liping An, Shifeng Huang, Xiaojuan Ji, Cheng Gong, Chengfu Yuan, Linghuan Zhang, Wei Liu, Bo Huang, Yixiao Feng, Bo Zhang, Rex C Haydon, Hue H Luu, Russell R Reid, Michael J Lee, Jennifer Moriatis Wolf, Zebo Yu, Tong-Chuan He
Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells that can undergo self-renewal and differentiate into multi-lineages. Bone marrow stromal stem cells (BMSCs) represent one of the most commonly-used MSCs. In order to overcome the technical challenge of maintaining primary BMSCs in long-term culture, here we seek to establish reversibly immortalized mouse BMSCs (imBMSCs). By exploiting CRISPR/Cas9-based homology-directed-repair (HDR) mechanism, we target SV40T to mouse Rosa26 locus and efficiently immortalize mouse BMSCs (i...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312637/notch-signaling-negatively-regulates-bmp9-induced-osteogenic-differentiation-of-mesenchymal-progenitor-cells-by-inhibiting-junb-expression
#13
Nan Wang, Wei Liu, Tao Tan, Chao-Qun Dong, Duan-Yang Lin, Jun Zhao, Chang Yu, Xiao-Ji Luo
Although interaction between BMP and Notch signaling has been demonstrated to be crucial for osteogenic differentiation of mesenchymal stem cells (MSCs), the precise molecular mechanism remains unknown. Here, we show that Notch intracellular domain (NICD) overexpression inhibits BMP9-induced C3H10T1/2 cell osteogenesis in vivo and in vitro . Our results show that activated Notch signaling results in down-regulation of Runx2 and early osteogenesis differentiation factors, without affecting p-Smad1/5/8 expression, and that blocking Notch signaling with DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) significantly increases p-Smad1/5/8 expression...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29259971/alk1fc-suppresses-the-human-prostate-cancer-growth-in-in-vitro-and-in-vivo-preclinical-models
#14
Letizia Astrologo, Eugenio Zoni, Sofia Karkampouna, Peter C Gray, Irena Klima, Joël Grosjean, Marie J Goumans, Lukas J A C Hawinkels, Gabri van der Pluijm, Martin Spahn, George N Thalmann, Peter Ten Dijke, Marianna Kruithof-de Julio
Prostate cancer is the second most common cancer in men and lethality is normally associated with the consequences of metastasis rather than the primary tumor. Therefore, targeting the molecular pathways that underlie dissemination of primary tumor cells and the formation of metastases has a great clinical value. Bone morphogenetic proteins (BMPs) play a critical role in tumor progression and this study focuses on the role of BMP9- A ctivin receptor- L ike K inase 1 and 2 (ALK1 and ALK2) axis in prostate cancer...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29223735/targeting-secreted-cytokine-bmp9-gates-the-attenuation-of-hepatic-fibrosis
#15
Peng Li, Yongyun Li, Liqi Zhu, Zhi Yang, Jie He, Lihua Wang, Qingfeng Shang, Hui Pan, Huixue Wang, Xiong Ma, Bin Li, Xianqun Fan, Shengfang Ge, Renbing Jia, He Zhang
Liver fibrosis is overly exuberant wound healing that leads to portal hypertension or liver cirrhosis. Recent studies have demonstrated the functions of bone morphogenetic protein 9 (BMP9) in liver fibrosis, and thus, targeting liver-specific BMP9 abnormalities will become an attractive approach for developing therapeutics to treat liver fibrosis. Here, we reveal that BMP9 serves as a valuable serum diagnostic indicator and efficient therapeutic target to attenuate liver fibrogenesis. Our analysis of biopsies from liver fibrotic patients revealed that higher BMP9 levels accompanied advanced stages of liver fibrosis...
March 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29073723/bmp9-cox-2-axial-mediates-high-phosphate-induced-calcification-in-vascular-smooth-muscle-cells-via-wnt-%C3%AE-catenin-pathway
#16
Fang He, Han Wang, Wen-Yan Ren, Yan Ma, Yun-Peng Liao, Jia-Hui Zhu, Jin Cui, Zhong-Liang Deng, Yu-Xi Su, Hua Gan, Bai-Cheng He
Vascular calcification is a notable risk factor for cardiovascular system. High phosphate can induce calcification in vascular smooth muscle cells (VSMCs), but the detail mechanism underlying this process remains unclear. In the present study, we determined the relationship between high phosphate and bone morphogenetic protein 9 (BMP9) in VSMCs, the effect of BMP9 on calcification in VSMCs and the effect of COX-2 on BMP9 induced calcification in VSMCs, as well as the possible mechanism underlying this biological process...
March 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29039519/runx3-plays-an-important-role-in-mediating-the-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells
#17
Yufeng Wang, Qiaoling Feng, Caixia Ji, Xiaohua Liu, Li Li, Jinyong Luo
Although bone morphogenetic protein 9 (BMP9) is highly capable of promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo, the molecular mechanisms involved remain to be fully elucidated. Runt-related transcription factor (RUNX)3 is an essential regulator of osteoblast/chondrocyte maturation. However, the exact role of RUNX3 in BMP9 osteoinductive activity is unknown. In this study, we sought to investigate the functional role of RUNX3 in the BMP9-induced osteogenic differentiation of MSCs...
September 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28973643/tacrolimus-rescues-the-signaling-and-gene-expression-signature-of-endothelial-alk1-loss-of-function-and-improves-hht-vascular-pathology
#18
Santiago Ruiz, Pallavi Chandakkar, Haitian Zhao, Julien Papoin, Prodyot K Chatterjee, Erica Christen, Christine N Metz, Lionel Blanc, Fabien Campagne, Philippe Marambaud
Hereditary hemorrhagic telangiectasia (HHT) is a highly debilitating and life-threatening genetic vascular disorder arising from endothelial cell (EC) proliferation and hypervascularization, for which no cure exists. Because HHT is caused by loss-of-function mutations in bone morphogenetic protein 9 (BMP9)-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic value. We interrogated the whole-transcriptome in human umbilical vein ECs (HUVECs) and found that ALK1 signaling inhibition was associated with a specific pro-angiogenic gene expression signature, which included a significant elevation of DLL4 expression...
December 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28956179/mir-149-promotes-human-osteocarcinoma-progression-via-targeting-bone-morphogenetic-protein-9-bmp9
#19
Zikang Xie, Jianda Xu, Libo Peng, Yi Gao, Hong Zhao, Yuxing Qu
OBJECTIVES: To investigate the roles of miR-149 in the progression of human osteosarcoma (OS). RESULTS: miR-149 level was upregulated in tissues from OS patients more than in normal subjects. Cell proliferation and apoptosis assays revealed that miR-149 increased cell proliferation and inhibited cell apoptosis in OS cell line (MG63). An increase of Bcl-2 gene expression and a decrease of cleaved-caspase-3, and cleaved-PARP expression were observed in MG63 cells with transfection of miR-149...
September 27, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28955765/identification-of-ligand-selective-peptidic-actriib-antagonists-using-phage-display-technology
#20
Kotaro Sakamoto, Yoko Kanematsu-Yamaki, Yusuke Kamada, Masahiro Oka, Toshiyuki Ohnishi, Masanori Miwa, Taiji Asami, Hiroshi Inooka
ActRIIB (activin receptor type-2B) is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN), growth differentiation factor 11 (GDF11), and bone morphogenetic protein 9 (BMP9). Notably, the protein-protein interaction (PPI) between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia...
September 2017: Biochemistry and Biophysics Reports
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