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https://www.readbyqxmd.com/read/28627680/bmp%C3%A2-7-suppresses-excessive-scar-formation-by-activating-the-bmp%C3%A2-7-smad1-5-8-signaling-pathway
#1
Jingdong Guo, Quan Lin, Ying Shao, Li Rong, Duo Zhang
Scarring is the inevitable consequence of wound repair, which may cause significant physical and mental pain to patients when excessive. Bone morphogenetic protein‑7 (BMP‑7) has been proved to inhibit TGF‑β‑induced fibrosis in various tissues including dermal papilla cells. However, the effect of BMP‑7 on hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, has not been determined. To overcome this problem, the present study established a mouse model of thermal injury to investigate the inhibitory effects of BMP‑7 on scar formation...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28607086/specific-targeting-of-tgf-%C3%AE-family-ligands-demonstrates-distinct-roles-in-the-regulation-of-muscle-mass-in-health-and-disease
#2
Justin L Chen, Kelly L Walton, Adam Hagg, Timothy D Colgan, Katharine Johnson, Hongwei Qian, Paul Gregorevic, Craig A Harrison
The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs) encoding ligand-specific antagonists into the tibialis anterior (TA) muscles of C57BL/6 mice. Eight weeks after AAV injection, inhibition of activin A and activin B signaling produced moderate (∼20%), but significant, increases in TA mass, indicating that endogenous activins repress muscle growth...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28604383/pyruvate-controls-the-checkpoint-inhibitor-pd-l1-and-suppresses-t-cell-immunity
#3
Ryu Watanabe, Tsuyoshi Shirai, Hong Namkoong, Hui Zhang, Gerald J Berry, Barbara B Wallis, Benedikt Schaefgen, David G Harrison, Jennifer A Tremmel, John C Giacomini, Jörg J Goronzy, Cornelia M Weyand
Patients with coronary artery disease (CAD) are at high risk for reactivation of the varicella zoster virus (VZV) and development of herpes zoster (HZ). Here, we found that macrophages from patients with CAD actively suppress T cell activation and expansion, leading to defective VZV-specific T cell immunity. Monocyte-derived and plaque-infiltrating macrophages from patients with CAD spontaneously expressed high surface density of the immunoinhibitory ligand programmed death ligand-1 (PD-L1), thereby providing negative signals to programmed death-1+ (PD-1+) T cells...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28602124/composite-scaffolds-of-mineralized-natural-extracellular-matrix-on-true-bone-ceramic-induce-bone-regeneration-via-smad1-5-8-and-erk1-2-pathways
#4
Tingfang Sun, Sheng Yao, Man Liu, Yushi Yang, Yanhui Ji, Wei Cui, Yanzhen Qu, Xiao-Dong Guo
A stem cell-derived mineralized extracellular matrix (ECM) may be a good strategy to endow scaffolds with a bone microenvironment, thus inducing bone regeneration. However, it also faces some challenges, such as limited cell number, additional wound for autologous cell isolation, and time consumption of cell expansion. In this study, we designed a novel tissue-derived ECM scaffold fabricated by depositing porcine small intestinal submucosa (SIS) ECM on true bone ceramic (TBC), which was followed by mineralization treatment (mSIS/TBC)...
June 10, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28601662/inhibition-of-mir-32-activity-promoted-emt-induced-by-pm2-5-exposure-through-the-modulation-of-the-smad1-mediated-signaling-pathways-in-lung-cancer-cells
#5
Dan Yang, Mingyue Ma, Weiqiang Zhou, Biao Yang, Chunling Xiao
Epithelial mesenchymal transition (EMT) is a crucial morphological event during tumor progression. The present study reported that EMT could be triggered by airborne fine particulate matter (PM) with a mean diameter of less than 2.5 μm (PM2.5) in human lung cancer cells. We also aimed to elucidate the possible mechanisms of these processes. The results showed that treatment with PM2.5 promoted the activity of the SMAD family member 1 (Smad1)-mediated signaling pathway and downregulated the expression of the inhibitory Smad proteins Smad6 and Smad7 in lung cancer cells...
May 30, 2017: Chemosphere
https://www.readbyqxmd.com/read/28595632/a-comparison-of-gene-expression-profiles-in-patients-with-coronary-artery-disease-type-2-diabetes-and-their-coexisting-conditions
#6
Rui Gong, Menghui Chen, Cuizhao Zhang, Manli Chen, Haibin Li
BACKGROUND: To support a hypothesis that there is an intrinsic interplay between coronary artery disease (CAD) and type 2 diabetes (T2D), we used RNA-seq to identify unique gene expression signatures of CAD, T2D, and coexisting conditions. METHODS: After transcriptome sequencing, differential expression analysis was performed between each disordered state and normal control group. By comparing gene expression profiles of CAD, T2D, and coexisting conditions, common and specific patterns of each disordered state were displayed...
June 8, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28590142/intra-amniotic-soluble-endoglin-impairs-lung-development-in-neonatal-rats
#7
Santhosh T Somashekar, Ibrahim Sammour, Jian Huang, Juan Dominguez-Bendala, Ricardo Pastori, Silvia Alvarez-Cubela, Eneida Torres, Shu Wu, Karen C Young
Soluble endoglin (sENG) is increased in the amniotic fluid of mothers with pre-eclampsia and chorioamnionitis. Preterm infants born to mothers with these disorders have an increased risk of aberrant lung development. Whether this increased risk is secondary to elevated sENG levels is unclear. The objective of this study was to determine whether intrauterine exposure to an adenovirus over-expressing sENG impairs neonatal lung angiogenesis by modulating lung eNOS signaling. Pregnant Sprague-Dawley rats were randomly assigned to receive ultrasound guided intra-amniotic injections of adenovirus over-expressing sENG (Ad-sENG) or control adenovirus (Ad-control) on embryonic day 17 (E17)...
June 7, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28589900/mir-26a-contributes-to-the-pdgf-bb-induced-phenotypic-switch-of-vascular-smooth-muscle-cells-by-suppressing-smad1
#8
Xiaoyan Yang, Mei Dong, Hao Wen, Xiaoling Liu, Meng Zhang, Lianyue Ma, Cheng Zhang, Xiaorong Luan, Huixia Lu, Yun Zhang
The phenotypic switch of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, such as atherosclerosis and post-angioplasty restenosis. Small non-coding microRNAs (miRNAs) have emerged as critical modulators of VSMC function. In the present study, miR-26a was significantly increased in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB) and in arteries with neointimal lesion formation. Moreover, we demonstrated that miR-26a regulates the expression of VSMC differentiation marker genes such as α-smooth muscle actin (α-SMA), calponin and smooth muscle myosin heavy chain (SM-MHC) in PDGF-BB-treated VSMCs...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588028/the-lysine-methyltransferase-smyd2-methylates-the-kinase-domain-of-type-ii-receptor-bmpr2-and-stimulates-bone-morphogenetic-protein-signaling
#9
Shuman Gao, Zhiqiang Wang, Wencai Wang, Xueli Hu, Peilin Chen, Jiwen Li, Xin Hua Feng, Jiemin Wong, James X Du
Lysine methylation of chromosomal and nuclear proteins is a well-known mechanism of epigenetic regulation, but relatively little is known about the role of this protein modification in signal transduction. Using an RNAi-based functional screening of the SMYD family of lysine methyltransferases (KMTs), we identified SMYD2 as a KMT essential for robust bone morphogenic protein (BMP)- but not TGFβ-induced target gene expression in HaCaT keratinocyte cells. A role for SMYD2 in BMP-induced gene expression was confirmed by shRNA knockdown and CRISPR/Cas9-mediated knockout of SMYD2...
June 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28578012/smad1-5-mediates-bone-morphogenetic-protein-2-induced-up-regulation-of-bambi-expression-in-human-granulosa-lutein-cells
#10
Long Bai, Hsun-Ming Chang, Jung-Chien Cheng, Christian Klausen, Guiyan Chu, Peter C K Leung, Gongshe Yang
Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is a transforming growth factor β (TGF-β) type I receptor antagonist that negatively regulates TGF-β and bone morphogenetic protein (BMP) signaling. BAMBI has been shown to be regulated by TGF-β signaling; however, whether BAMBI can be regulated by BMP signaling remains to be determined. The aim of this study was to investigate the effect of BMP2 on the regulation of BAMBI expression in human granulosa-lutein cells and the underlying mechanisms...
May 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28569204/tgf%C3%AE-1-induced-smad2-3-and-smad1-5-phosphorylation-are-both-alk5-kinase-dependent-in-primary-chondrocytes-and-mediated-by-tak1-kinase-activity
#11
Arjan van Caam, Wojciech Madej, Amaya Garcia de Vinuesa, Marie-José Goumans, Peter Ten Dijke, Esmeralda Blaney Davidson, Peter van der Kraan
BACKGROUND: Dysregulated transforming growth factor β (TGFβ) signaling is implicated in osteoarthritis development, making normalizing TGFβ signaling a possible therapy. Theoretically, this can be achieved with small molecule inhibitors specifically targeting the various TGFβ receptors and downstream mediators. In this study we explore in primary chondrocytes the use of small molecule inhibitors to target TGFβ-induced pSmad1/5/9-, pSmad2/3- and TGFβ-activated kinase 1 (TAK1)-dependent signaling...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28558704/genome-wide-network-based-pathway-analysis-of-csf-t-tau-a%C3%AE-1-42-ratio-in-the-adni-cohort
#12
Wang Cong, Xianglian Meng, Jin Li, Qiushi Zhang, Feng Chen, Wenjie Liu, Ying Wang, Sipu Cheng, Xiaohui Yao, Jingwen Yan, Sungeun Kim, Andrew J Saykin, Hong Liang, Li Shen
BACKGROUND: The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ1-42 are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks...
May 30, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28542453/extracellular-calcium-promotes-bone-formation-from-bone-marrow-mesenchymal-stem-cells-by-amplifying-the-effects-of-bmp-2-on-smad-signalling
#13
Rubén Aquino-Martínez, Natalia Artigas, Beatriz Gámez, José Luis Rosa, Francesc Ventura
Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28530121/glucocorticoids-retain-bi-potent-fibroblast-progenitors-during-alveolar-septation-in-mice
#14
Stephen E McGowan, Diann M McCoy
Glucocorticoids have been widely used and exert pleiotropic effects on alveolar structure and function, but do not improve the long-term clinical outcomes for patients with bronchopulmonary dysplasia, emphysema, or interstitial lung diseases. Treatments which foster alveolar regeneration could substantially improve the long-term outcomes for such patients. One approach to alveolar regeneration is to stimulate and guide intrinsic alveolar progenitors along developmental pathways used during secondary septation...
May 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28509082/atg7-mediated-autophagy-is-involved-in-the-neural-crest-cell-generation-in-chick-embryo
#15
Guang Wang, En-Ni Chen, Chang Liang, Jianxin Liang, Lin-Rui Gao, Manli Chuai, Andrea Münsterberg, Yongping Bao, Liu Cao, Xuesong Yang
Autophagy plays a very important role in numerous physiological and pathological events. However, it still remains unclear whether Atg7-induced autophagy is involved in the regulation of neural crest cell production. In this study, we found the co-location of Atg7 and Pax7(+) neural crest cells in early chick embryo development. Upregulation of Atg7 with unilateral transfection of full-length Atg7 increased Pax7(+) and HNK-1(+) cephalic and trunk neural crest cell numbers compared to either Control-GFP transfection or opposite neural tubes, suggesting that Atg7 over-expression in neural tubes could enhance the production of neural crest cells...
May 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28494020/pannexin-3-regulates-proliferation-and-differentiation-of-odontoblasts-via-its-hemichannel-activities
#16
Tsutomu Iwamoto, Takashi Nakamura, Masaki Ishikawa, Keigo Yoshizaki, Asuna Sugimoto, Hiroko Ida-Yonemochi, Hayato Ohshima, Masahiro Saito, Yoshihiko Yamada, Satoshi Fukumoto
Highly coordinated regulation of cell proliferation and differentiation contributes to the formation of functionally shaped and sized teeth; however, the mechanism underlying the switch from cell cycle exit to cell differentiation during odontogenesis is poorly understood. Recently, we identified pannexin 3 (Panx3) as a member of the pannexin gap junction protein family from tooth germs. The expression of Panx3 was predominately localized in preodontoblasts that arise from dental papilla cells and can differentiate into dentin-secreting odontoblasts...
2017: PloS One
https://www.readbyqxmd.com/read/28489883/bmp-7-induces-apoptosis-in-human-germinal-center-b-cells-and-is-influenced-by-tgf-%C3%AE-receptor-type-i-alk5
#17
Lise K Bollum, Kanutte Huse, Morten P Oksvold, Baoyan Bai, Vera I Hilden, Lise Forfang, Sun Ok Yoon, Sébastien Wälchli, Erlend B Smeland, June H Myklebust
Selection and maturation of B cells into plasma cells producing high-affinity antibodies occur in germinal centers (GC). GCs form transiently in secondary lymphoid organs upon antigen challenge, and the GC reaction is a highly regulated process. TGF-β is a potent negative regulator, but the influence of other family members including bone morphogenetic proteins (BMPs) is less known. Studies of human peripheral blood B lymphocytes showed that BMP-6 suppressed plasmablast differentiation, whereas BMP-7 induced apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28477026/mir-199a-3p-suppresses-proliferation-and-invasion-of-prostate-cancer-cells-by-targeting-smad1
#18
Feng Qu, Jinyu Zheng, Weidong Gan, Huibo Lian, Hua He, Wuping Li, Tian Yuan, Yaling Yang, Xiaogong Li, Changwei Ji, Xiang Yan, Linfeng Xu, Hongqian Guo
OBJECTIVES: This study was intended to analyze effects of miR-199a-3p and Smad1 on proliferation, migration and invasion of prostate cancer (PCa) cells. RESULTS: MiR-199a-3p was significantly decreased in PCa tissues in comparison to that in adjacent normal tissues (P < 0.05). Over-expressed miR-199a-3p markedly suppressed proliferation and invasion of PCa cells (P < 0.05). MiR-199a-3p was negatively correlated with Smad1 expression, and overexpression of Smad1 could antagonize the effects of miR-199a-3p on PCa cells...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28469774/effects-of-altered-cxcl12-cxcr4-axis-on-bmp2-smad-runx2-osterix-axis-and-osteogenic-gene-expressions-during-osteogenic-differentiation-of-mscs
#19
Zhanghua Li, Wei Wang, Haijia Xu, Yu Ning, Weijun Fang, Wen Liao, Ji Zou, Yi Yang, Ningsheng Shao
This study investigated the effects of altered CXCL12/CXCR4 axis on the bone morphogenetic protein 2 (BMP-2)/Smad/runt-related transcription factor 2 (Runx2)/Osterix (Osx) signal axis and osteogenic gene expression during osteogenic differentiation of mesenchymal stem cells (MSCs), to gain understanding of the link between migration and osteogenic differentiation signal axis and MSCs osteogenic differentiation mechanisms. The pHBAd-MCMV- CXCL12-GFP vector (Ad-CXCL12) was constructed and quantitative polymerase chain reaction (qPCR)/western blotting used to determine CXCL12 expression in Ad-CXCL12-transfected MSCs...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28468941/aberrant-caveolin-1-mediated-smad-signaling-and-proliferation-identified-by-analysis-of-adenine-474-deletion-mutation-c-474dela-in-patient-fibroblasts-a-new-perspective-on-the-mechanism-of-pulmonary-hypertension
#20
Glenn Marsboom, Zhenlong Chen, Yang Yuan, Yanmin Zhang, Chinnaswamy Tiruppathi, James E Loyd, Eric D Austin, Roberto F Machado, Richard D Minshall, Jalees Rehman, Asrar B Malik
A heterozygous caveolin-1 c.474delA mutation has been identified in a family with heritable pulmonary arterial hypertension (PAH). This frameshift mutation leads to a caveolin-1 protein that contains all known functional domains but has a change in only the final 20 amino acids of the C-terminus. Here we studied how this mutation alters caveolin-1 function, using patient-derived fibroblasts. Transmission electron microscopy showed that fibroblasts carrying the c.474delA mutation form typical caveolae. Expression of mutated caveolin-1 in caveolin-1-null mouse fibroblasts failed to induce formation of caveolae due to retention of the mutated protein in the endoplasmic reticulum...
May 1, 2017: Molecular Biology of the Cell
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