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https://www.readbyqxmd.com/read/28438754/smad1-5-is-required-for-erythropoietin-mediated-suppression-of-hepcidin-in-mice
#1
Chia-Yu Wang, Amanda B Core, Susanna Canali, Kimberly B Zumbrennen-Bullough, Sinan Ozer, Lieve Umans, An Zwijsen, Jodie L Babitt
Anemia suppresses liver hepcidin expression to supply adequate iron for erythropoiesis. Erythroferrone mediates hepcidin suppression by anemia, but its mechanism of action remains uncertain. The bone morphogenetic protein (BMP)-SMAD signaling pathway has a central role in hepcidin transcriptional regulation. Here, we explored the contribution of individual receptor-activated SMADs in hepcidin regulation and their involvement in erythroferrone suppression of hepcidin. In Hep3B cells, SMAD5 or SMAD1, but not SMAD8, knockdown inhibited hepcidin (HAMP) mRNA expression...
April 24, 2017: Blood
https://www.readbyqxmd.com/read/28427181/metformin-inhibits-alk1-mediated-angiogenesis-via-activation-of-ampk
#2
Ying Ying, Takashi Ueta, Shanshan Jiang, Hui Lin, Yuanyuan Wang, Demetrios Vavvas, Rong Wen, Ye-Guang Chen, Zhijun Luo
Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28397746/non-anticoagulant-heparins-are-hepcidin-antagonists-for-the-treatment-of-anemia
#3
REVIEW
Maura Poli, Michela Asperti, Paola Ruzzenenti, Annamaria Naggi, Paolo Arosio
The peptide hormone hepcidin is a key controller of systemic iron homeostasis, and its expression in the liver is mainly regulated by bone morphogenetic proteins (BMPs), which are heparin binding proteins. In fact, heparins are strong suppressors of hepcidin expression in hepatic cell lines that act by inhibiting the phosphorylation of SMAD1/5/8 proteins elicited by the BMPs. The inhibitory effect of heparins has been demonstrated in cells and in mice, where subcutaneous injections of non-anticoagulant heparins inhibited liver hepcidin expression and increased iron bioavailability...
April 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28389444/bone-morphogenetic-protein-based-therapeutic-approaches
#4
Jonathan W Lowery, Vicki Rosen
Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor (TGF)-β family of ligands and exert most of their effects through the canonical effectors Smad1, 5, and 8. Appropriate regulation of BMP signaling is critical for the development and homeostasis of numerous human organ systems. Aberrations in BMP pathways or their regulation are increasingly associated with diverse human pathologies, and there is an urgent and growing need to develop effective approaches to modulate BMP signaling in the clinic...
April 7, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28377490/biological-role-and-therapeutic-targeting-of-tgf-%C3%AE-3-in-glioblastoma
#5
Katharina Seystahl, Alexandros Papachristodoulou, Isabel Burghardt, Hannah Schneider, Kathy Hasenbach, Michel Janicot, Patrick Roth, Michael Weller
Transforming growth factor (TGF)-β contributes to the malignant phenotype of glioblastoma by promoting invasiveness and angiogenesis and creating an immunosuppressive microenvironment. So far, TGF-β1 and TGF-β2 isoforms have been considered to act in a similar fashion without isoform-specific function in glioblastoma. A pathogenic role for TGF-β3 in glioblastoma has not been defined yet. Here we studied the expression and functional role of endogenous and exogenous TGF-β3 in glioblastoma models. TGF-β3 mRNA is expressed in human and murine long-term glioma cell lines as well as in human glioma-initiating cell cultures with expression levels lower than TGF-β1 or TGF-β2 in most cell lines...
April 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28357470/differential-molecular-regulation-of-processing-and-membrane-expression-of-type-i-bmp-receptors-implications-for-signaling
#6
Tal Hirschhorn, Michal Levi-Hofman, Oded Danziger, Nechama I Smorodinsky, Marcelo Ehrlich
The Type-I bone morphogenetic protein receptors (BMPRs), BMPR1A and BMPR1B, present the highest sequence homology among BMPRs, suggestive of functional similitude. However, sequence elements within their extracellular domain, such as signal sequence or N-glycosylation motifs, may result in differential regulation of biosynthetic processing and trafficking and in alterations to receptor function. We show that (i) BMPR1A and the ubiquitous isoform of BMPR1B differed in mode of translocation into the endoplasmic reticulum; and (ii) BMPR1A was N-glycosylated while BMPR1B was not, resulting in greater efficiency of processing and plasma membrane expression of BMPR1A...
March 29, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28352232/dickkopf-3-upregulates-vegf-in-cultured-human-endothelial-cells-by-activating-activin-receptor-like-kinase-1-alk1-pathway
#7
Carla L Busceti, Simona Marchitti, Franca Bianchi, Paola Di Pietro, Barbara Riozzi, Rosita Stanzione, Milena Cannella, Giuseppe Battaglia, Valeria Bruno, Massimo Volpe, Francesco Fornai, Ferdinando Nicoletti, Speranza Rubattu
Dkk-3 is a member of the dickkopf protein family of secreted inhibitors of the Wnt pathway, which has been shown to enhance angiogenesis. The mechanism underlying this effect is currently unknown. Here, we used cultured HUVECs to study the involvement of the TGF-β and VEGF on the angiogenic effect of Dkk-3. Addition of hrDkk-3 peptide (1 or 10 ng/ml) to HUVECs for 6 or 12 h enhanced the intracellular and extracellular VEGF protein levels, as assessed by RTPCR, immunoblotting, immunocytochemistry and ELISA...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28351832/gonad-related-factors-promote-muscle-performance-gain-during-postnatal-development-in-male-and-female-mice
#8
Vanessa Ueberschlag-Pitiot, Amalia Stantzou, Julien Messéant, Megane Lemaitre, Daniel J Owens, Philippe Noirez, Pauline Roy, Onnik Agbulut, Daniel Metzger, Arnaud Ferry
In order to better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analysed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-month old male and female castrated mice, as compared to age- and sex-matched intact mice, without alteration in neuromuscular transmission...
March 28, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28327634/scleraxis-is-required-for-maturation-of-tissue-domains-for-proper-integration-of-the-musculoskeletal-system
#9
Yuki Yoshimoto, Aki Takimoto, Hitomi Watanabe, Yuji Hiraki, Gen Kondoh, Chisa Shukunami
Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is expressed persistently in tendons/ligaments, but transiently in entheseal cartilage. In this study, we generated a novel Scx(Cre) knock-in (KI) allele, by in-frame replacement of most of Scx exon 1 with Cre recombinase (Cre), to drive Cre expression using Scx promoter and to inactivate the endogenous Scx. Reflecting the intensity and duration of endogenous expression, Cre-mediated excision occurs in tendinous and ligamentous tissues persistently expressing Scx...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298490/aberrant-caveolin-1-mediated-smad-signaling-and-proliferation-identified-by-analysis-of-adenine-474-deletion-mutation-c-474dela-in-patient-fibroblasts-a-new-perspective-in-the-mechanism-of-pulmonary-hypertension
#10
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 caveolin-1 protein that contains all known functional domains but has a change only in 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 formed 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...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28298362/negative-regulation-of-smad1-pathway-and-collagen-iv-expression-by-store-operated-ca2-entry-in-glomerular-mesangial-cells
#11
Peiwen Wu, Yuezhong Ren, Yuhong Ma, Yanxia Wang, Hui Jiang, Sarika Chaudhari, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca2+ entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high glucose-increased Smad1 protein content...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28288971/activation-of-cd137-signaling-promotes-angiogenesis-in-atherosclerosis-via-modulating-endothelial-smad1-5-nfatc1-pathway
#12
Jiayi Weng, Cuiping Wang, Wei Zhong, Bo Li, Zhongqun Wang, Chen Shao, Yao Chen, Jinchuan Yan
BACKGROUND: Excessive angiogenesis is a key feature of vulnerable atherosclerotic plaques, and is considered an independent predictor of cardiovascular risk. CD137 signaling has previously been shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulating angiogenesis has not been reported. METHODS AND RESULTS: Apolipoprotein E-deficient (ApoE(-/-)) mice were used as the in vivo model of atherosclerosis. Masson and immunohistochemical analysis of atherosclerotic plaques and Matrigel plug assay were used to evaluate the angiogenesis...
March 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28259395/short-communication-tryptic-%C3%AE-casein-hydrolysate-modulates-enteric-nervous-system-development-in-primary-culture
#13
F Cossais, I Clawin-Rädecker, P C Lorenzen, M Klempt
The intestinal tract of the newborn is particularly sensitive to gastrointestinal disorders, such as infantile diarrhea or necrotizing colitis. Perinatal development of the gut also encompasses the maturation of the enteric nervous system (ENS), a main regulator of intestinal motility and barrier functions. It was recently shown that ENS maturation can be enhanced by nutritional factors to improve intestinal maturation. Bioactivity of milk proteins is often latent, requiring the release of bioactive peptides from inactive native proteins...
May 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28240243/smad3-and-smad4-have-a-more-dominant-role-than-smad2-in-tgf%C3%AE-induced-chondrogenic-differentiation-of-bone-marrow-derived-mesenchymal-stem-cells
#14
Laurie M G de Kroon, Roberto Narcisi, Guus G H van den Akker, Elly L Vitters, Esmeralda N Blaney Davidson, Gerjo J V M van Osch, Peter M van der Kraan
To improve cartilage formation by bone marrow-derived mesenchymal stem cells (BMSCs), the signaling mechanism governing chondrogenic differentiation requires better understanding. We previously showed that the transforming growth factor-β (TGFβ) receptor ALK5 is crucial for chondrogenesis induced by TGFβ. ALK5 phosphorylates SMAD2 and SMAD3 proteins, which then form complexes with SMAD4 to regulate gene transcription. By modulating the expression of SMAD2, SMAD3 and SMAD4 in human BMSCs, we investigated their role in TGFβ-induced chondrogenesis...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28235949/bmp4-inhibits-pdgf-induced-proliferation-and-collagen-synthesis-via-pka-mediated-inhibition-of-calpain-2-in-pulmonary-artery-smooth-muscle-cells
#15
PengCheng Cai, Laszlo Kovacs, Sam Dong, Guangyu Wu, Yunchao Su
In the present study, we investigated the effect of bone morphogenetic protein 4 (BMP4) on PDGF-induced proliferation and collagen synthesis in PASMCs. Normal human PASMCs were incubated with and without PDGF-BB in the absence and presence of BMP4 for 0.5 to 24 h. Then the protein levels of collagen-I, p-Smad2/3, p-Smad1/5, and intracellular active TGFβ1, calpain activity and cell proliferation were measured. The results showed that BMP4 induced an increase in p-Smad1/5 but had no effect on the protein levels of collagen-I, p-Smad2/3, and intracellular active TGFβ1, and calpain activity in PASMCs...
February 24, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28219352/retinoic-acid-promotes-expression-of-germline-specific-genes-in-chicken-blastoderm-cells-by-stimulating-smad1-5-phosphorylation-in-a-feeder-free-culture-system
#16
Xiaochuan Tang, Shiyong Xu, Hongpeng Zhang, Qing Chen, Rongyang Li, Wangjun Wu, Minli Yu, Honglin Liu
BACKGROUND: Producing transgenic chickens with chicken blastodermal cells (cBCs) is inefficient due to the extremely low germline transmission capacity of cBCs. As chicken primordial germ cells (PGCs) have been reported as an efficient method for producing transgenic chickens, the inefficiency of cBCs could potentially be resolved by inducing them to differentiate into germ cells. However, whether chemical inducers are able to enhance cBCs germline competence in vitro is unknown and the molecular mechanisms of differentiation of chicken pluripotent cells into germ cells are poorly understood...
February 20, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28213129/cyclic-compressive-stress-induced-scinderin-regulates-progress-of-developmental-dysplasia-of-the-hip
#17
Cheng-Long Wang, Hui Wang, Fei Xiao, Chuan-Dong Wang, Guo-Li Hu, Jun-Feng Zhu, Chao Shen, Bin Zuo, Yi-Min Cui, De Li, Yuan-Gao, Xiao-Ling Zhang, Xiao-Dong Chen
Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs). To analyze the effect of Ccs on DDH, we detected special genes in chondrocytes and osteoblasts. Results showed that Ccs downregulated chondrogenesis of ADTC5 in a concentration-dependent manner...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28202082/bone-morphogenetic-proteins-and-myostatin-pathways-key-mediator-of-human-sarcopenia
#18
Manuel Scimeca, Eleonora Piccirilli, Francesca Mastrangeli, Cecilia Rao, Maurizio Feola, Augusto Orlandi, Elena Gasbarra, Elena Bonanno, Umberto Tarantino
BACKGROUND: Sarcopenia, osteoporosis and osteoarthritis are the most frequent musculoskeletal disorders affecting older people. The main aim of this study was to test the hypothesis that the balance between BMPs and myostatin pathways regulates the age-related muscle degeneration in OP and OA patients. To this end, we investigated the relationship among the expression of BMP-2/4-7, myostatin and phosphorylated Smads1-5-8 and the muscle quality, evaluated in term of fibers atrophy and satellite cells activity...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28199984/autocrine-and-paracrine-stip1-signaling-promote-osteolytic-bone-metastasis-in-renal-cell-carcinoma
#19
Jiang Wang, Hongbo You, Jun Qi, Caihong Yang, Ye Ren, Hao Cheng
Bone metastases are responsible for some of the most devastating complications of renal cell carcinoma (RCC). However, pro-metastatic factors leading to the highly osteolytic characteristics of RCC bone metastasis have barely been explored. We previously developed novel bone-seeking RCC cell lines by the in vivo selection strategy and performed a comparative proteome analysis on their total cell lysate. Here, we focused on STIP1 (stress-induced phosphoprotein 1), the high up-regulated protein in the bone-seeking cells, and explored its clinical relevance and functions in RCC bone metastasis...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28155178/tumor-necrosis-factor-%C3%AE-and-transforming-growth-factor-%C3%AE-1-facilitate-differentiation-and-proliferation-of-tendon-derived-stem-cells-in-vitro
#20
Peilin Han, Qingbo Cui, Shulong Yang, Hao Wang, Peng Gao, Zhaozhu Li
OBJECTIVES: To investigate the effects of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) on the proliferation and differentiation of tendon-derived stem cells (TDSC). RESULTS: TNF-α inhibits the proliferation and tenogenic/osteogenic differentiation of TDSC but, after simultaneous or sequential treatment with TGF-β1 and TNF-α, the expression of tenogenic/osteogenic-related marker and proliferation of TDSC was significantly increased...
February 2, 2017: Biotechnology Letters
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