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https://www.readbyqxmd.com/read/29229532/inflammation-and-renal-fibrosis-recent-developments-on-key-signaling-molecules-as-potential-therapeutic-targets
#1
REVIEW
Wenshan Lv, George W Booz, Yangang Wang, Fan Fan, Richard J Roman
Chronic kidney disease (CKD) is a major public health issue. At the histological level, renal fibrosis is the final common pathway of progressive kidney disease irrespective of the initial injury. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Some of the inflammatory signaling molecules involved in CKD include: monocyte chemoattractant protein-1 (MCP-1), bradykinin B1 receptor (B1R), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNFα), transforming growth factor β (TGF-β), and platelet-derived growth factor (PDGF)...
December 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29228234/tgfbr2-inactivation-facilitates-cellular-plasticity-and-development-of-pten-null-prostate-cancer
#2
Wei Zhao, Peng Tan, Qingyuan Zhu, Adebusola Ajibade, Teng Long, Wenyong Long, Qingtian Li, Pinghua Liu, Bo Ning, Helen Y Wang, Rong-Fu Wang
Mutations in tumors can create a state of increased cellular plasticity that promotes resistance to treatment. Thus, there is an urgent need to develop novel strategies for identifying key factors that regulate cellular plasticity in order to combat resistance to chemotherapy and radiation treatment. Here we report that prostate epithelial cell reprogramming could be exploited to identify key factors required for promoting prostate cancer tumorigenesis and cellular plasticity. Deletion of phosphatase and tensin homolog (Pten) and transforming growth factor-beta receptor type 2 (Tgfbr2) may increase prostate epithelial cell reprogramming efficiency in vitro and cause rapid tumor development and early mortality in vivo...
December 8, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29221205/thrombospondin-1-modified-bone-marrow-mesenchymal-stem-cells-bmscs-promote-neurite-outgrowth-and-functional-recovery-in-rats-with-spinal-cord-injury
#3
Yujie Pu, Ke Meng, Chuanlong Gu, Linlin Wang, Xiaoming Zhang
Stem cell therapies are currently gaining momentum in the treatment of spinal cord injury (SCI). However, unsatisfied intrinsic neurite growth capacity constitutes significant obstacles for injured spinal cord repair and ultimately results in neurological dysfunction. The present study assessed the efficacy of thrombospondin-1 (TSP-1), a neurite outgrowth-promoting molecule, modified bone marrow mesenchymal stem cells (BMSCs) on promoting neurite outgrowth in vitro and in vivo of Oxygen-Glucose Deprivation (OGD) treated motor neurons and SCI rat models...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221155/cd109-released-from-human-bone-marrow-mesenchymal-stem-cells-attenuates-tgf-%C3%AE-induced-epithelial-to-mesenchymal-transition-and-stemness-of-squamous-cell-carcinoma
#4
Shufeng Zhou, Renzo Cecere, Anie Philip
Although there is increasing evidence that human bone marrow mesenchymal stem cells (hBM-MSCs) play an important role in cancer progression, the underlying mechanisms are poorly understood. Transforming growth factor β (TGF-β) is an important pro-metastatic cytokine. We have previously shown that CD109, a glycosylphosphatidylinositol-anchored protein, is a TGF-β co-receptor and a strong inhibitor of TGF-β signalling. Moreover, CD109 can be released from the cell surface. In the current study, we examined whether hBM-MSCs regulate the malignant properties of squamous cell carcinoma cells, and whether CD109 plays a role in mediating the effect of hBM-MSCs on cancer cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217273/ltbps-in-biology-and-medicine-ltbp-diseases
#5
REVIEW
Daniel B Rifkin, William J Rifkin, Lior Zilberberg
The latent transforming growth factor (TGF) β binding proteins (LTBP) are crucial mediators of TGFβ function, as they control growth factor secretion, matrix deposition, presentation and activation. Deficiencies in specific LTBP isoforms yield discrete phenotypes representing defects in bone, lung and cardiovascular development mediated by loss of TGFβ signaling. Additional phenotypes represent loss of unique TGFβ-independent features of LTBP effects on elastogenesis and microfibril assembly. Thus, the LTBPs act as sensors for the regulation of both growth factor activity and matrix function...
December 4, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29216915/rheumatoid-arthritis-bone-marrow-environment-supports-th17-response
#6
Ewa Kuca-Warnawin, Weronika Kurowska, Monika Prochorec-Sobieszek, Anna Radzikowska, Tomasz Burakowski, Urszula Skalska, Magdalena Massalska, Magdalena Plebańczyk, Barbara Małdyk-Nowakowska, Iwona Słowińska, Robert Gasik, Włodzimierz Maśliński
BACKGROUND: Rheumatoid arthritis (RA) is a systemic, autoimmune disease leading to joint destruction and ultimately disability. Bone marrow (BM) is an important compartment in RA, where pathological processes from "outside the joint" can occur. IL-17 is a cytokine that exerts proinflammatory effects and participates in the process of bone destruction. It is believed that IL-17 is involved in pathogenesis of RA. However, little is known about the biology of this cytokine in BM. In the present study we investigated Th17-related cytokines in RA BM...
December 8, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29216639/exendin-4-induces-bone-marrow-stromal-cells-migration-through-bone-marrow-derived-macrophages-polarization-via-pka-stat3-signaling-pathway
#7
Ning Wang, Jian Gao, Min Jia, Xue Ma, Zhanxiang Lei, Fei Da, Fei Yan, Huinan Zhang, Ying Zhou, Mingkai Li, Gonghao He, Jingru Meng, Xiaoxing Luo
BACKGROUND/AIMS: The synthesis and degradation processes involved in bone remodeling are critically regulated by osteoblasts and osteoclasts. The GLP-1 receptor agonist Exendin-4 is beneficial for osteoblast differentiation and increases the number of osteoblasts. METHODS: We constructed an ovariectomized model to evaluate the impact of Exendin-4 on bone formation in osteoporosis. A macrophage-depleted model was also created to investigate the effect of macrophages on bone formation...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29216525/high-refined-carbohydrate-diet-promotes-detrimental-effects-on-alveolar-bone-and-femur-microarchitecture
#8
C C Montalvany-Antonucci, M C Zicker, S Macari, T S F Pereira, I M A Diniz, I Andrade, A V M Ferreira, T A Silva
The impact of high-refined carbohydrate (HC) diet on fat accumulation, adipokines secretion and systemic inflammation is well described. However, it remains unclear whether these processes affect bone remodeling. OBJECTIVE: To investigate the effects of HC diet in the alveolar bone and femur parameters. METHODS: BalbC mice were fed with conventional chow or HC diet for 12 weeks. After experimental time maxillae, femur, blood and white adipose tissue samples were collected...
November 28, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29215756/downregulation-of-regulatory-t-cell-function-in-patients-with-delayed-fracture-healing
#9
Hui Jiang, Yunfan Ti, Yicun Wang, Jun Wang, Menghan Chang, Jianning Zhao, Guojing Sun
Bone fracture healing is a multistage regenerative process that requires the collaboration of various cell types, with approximately 5% - 10% of fractures not healing properly. Accumulating evidence suggests that dysregulations in the immune system are associated with defective healing. In a cohort of 30 bone fracture patients between 50 and 62 years of age, 8 patients displayed delayed healing. Compared to the 22 normal healing patients, these 8 delayed healing patients presented significantly lower frequencies of CD4+ CD25hi Foxp3+ canonical regulatory T cells immediately following bone fracture and early on during the healing process...
December 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29211121/evolution-of-periodontal-disease-immune-response-and-rank-rankl-opg-system
#10
Fabrício Gibertoni, Meire Ellen Ligia Sommer, Marcelo Augusto Marretto Esquisatto, Maria Esméria Corezola do Amaral, Camila Andrea de Oliveira, Thiago Antônio Moretti de Andrade, Fernanda Aparecida Sampaio Mendonça, Milton Santamaria-Jr, Maíra Felonato
The aim of this study was to evaluate markers of bone loss and immune response present in evolution of periodontal disease. One hundred and two Wistar rats were divided into three animals groups: PD0, without ligation and PD15 days and PD60 days, submitted to ligation placement with a sterile 3-0 silk cord in the cervical region of the upper first molar on both sides. Samples were obtained from the gingival tissue for histomorphometric analysis, immunohistochemical analysis of RANK, RANKL, OPG, characterization of the inflammatory infiltrate, quantification of nitric oxide, MCP-1, RANTES, IP10 chemokines, and expression of the TGF-b1, VEG, and bFGF...
November 2017: Brazilian Dental Journal
https://www.readbyqxmd.com/read/29209333/inhibition-of-acute-graft-versus-host-disease-with-retention-of-graft-versus-tumor-effects-by-dimethyl-fumarate
#11
Jingjing Han, Shoubao Ma, Huanle Gong, Shuangzhu Liu, Lei Lei, Bo Hu, Yang Xu, Haiyan Liu, Depei Wu
Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29208173/transforming-growth-factor-%C3%AE-1-gene-polymorphism-and-osteoporosis-in-postmenopausal-egyptian-women
#12
Inass M Taha, Azza M Abdu Allah, Maha A F Hamoudah, S Justin Carlus
Transforming growth factor-β1 (TGF-β1) is a wide spread bone matrix protein that affect the function, formation and cell-cell interactions of osteoclasts and osteoblasts to regulate bone remodeling and sustain adequate bone mass. The aim of this study is to evaluate the role of the two polymorphism of transforming growth factor-β1 T869C and C-509T in developing osteoporosis in postmenopausal Egyptian women. This study was performed on 138 postmenopausal osteoporosis/osteopenic women and 128 postmenopausal female control group...
November 30, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29207055/therapeutic-effects-of-conditioned-medium-from-bone-marrow-derived-mesenchymal-stem-cells-on-epithelial-mesenchymal-transition-in-a549-cells
#13
Xin Wang, Jun-Ling Gao, Man-Man Zhao, Hui-Xing Zhu, Yan-Xia Tian, Ran Li, Xiao-Hua Jiang, Lei Yu, Jing-Rui Tian, Jian-Zhong Cui
Pulmonary fibrosis (PF) is a chronic lung disease. The transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to be a modulator of the molecular aspects of the fibrosis pathway. However, it is still unknown as to whether the conditioned medium from BMSCs (BMSCs-CM) inhibits the epithelial-mesenchymal transition (EMT) process. This study confirmed the hypothesis that BMSCs-CM exerts an anti-fibrotic effect on human type II alveolar epithelial cells (A549) by suppressing the phosphorylation of Smad3...
November 24, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29198724/monoallelic-bmp2-variants-predicted-to-result-in-haploinsufficiency-cause-craniofacial-skeletal-and-cardiac-features-overlapping-those-of-20p12-deletions
#14
Tiong Yang Tan, Claudia Gonzaga-Jauregui, Elizabeth J Bhoj, Kevin A Strauss, Karlla Brigatti, Erik Puffenberger, Dong Li, LiQin Xie, Nanditha Das, Ioanna Skubas, Ron A Deckelbaum, Virginia Hughes, Susannah Brydges, Sarah Hatsell, Chia-Jen Siao, Melissa G Dominguez, Aris Economides, John D Overton, Valerie Mayne, Peter J Simm, Bryn O Jones, Stefanie Eggers, Gwenaël Le Guyader, Fanny Pelluard, Tobias B Haack, Marc Sturm, Angelika Riess, Stephan Waldmueller, Michael Hofbeck, Katharina Steindl, Pascal Joset, Anita Rauch, Hakon Hakonarson, Naomi L Baker, Peter G Farlie
Bone morphogenetic protein 2 (BMP2) in chromosomal region 20p12 belongs to a gene superfamily encoding TGF-β-signaling proteins involved in bone and cartilage biology. Monoallelic deletions of 20p12 are variably associated with cleft palate, short stature, and developmental delay. Here, we report a cranioskeletal phenotype due to monoallelic truncating and frameshift BMP2 variants and deletions in 12 individuals from eight unrelated families that share features of short stature, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease...
November 23, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29197953/prolonged-use-of-alendronate-alters-the-biology-of-cranial-repair-in-estrogen-deficient-rats-associated-simultaneous-immunohistochemical-expression-of-tgf-%C3%AE-1-%C3%AE-er-and-bmpr1b
#15
Allan Fernando Giovanini, Giuliene Nunes de Sousa Passoni, Isabella Göhringer, Tatiana Miranda Deliberador, João Cesar Zielak, Carmem Lucia Muller Storrer, Thais Andrade Costa-Casagrande, Rafaela Scariot
OBJECTIVES: TGF-β1 is a cytokine that may induce both osteoneogenesis through Runx-2 or fibrosis via the transcription of α-smooth muscle actin (α-SMA). Because it has been previously known that alendronate increases the level of TGF-β1 and that under the usual condition of bone metabolism the estrogen may prevent the fibrotic effect of TGF-β1, the aim of this study was to evaluate if alendronate alters the cellular differentiation process post calvarial surgery in estrogen-deficient specimens...
December 2, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29196107/distribution-of-smad-mrna-and-proteins-in-the-rat-brain
#16
Takayuki Nakajima, Ryusuke Hata, Yuji Kunieda, Tomohiro Kondo
Smad proteins are known to transduce the action of TGF-β superfamily proteins including TGF-βs, activins, and bone morphogenetic proteins (BMPs). In this study, we examined the expression of Smad1, -2, -3, -4, -5, and -8 mRNA in the rat brain by means of RT-PCR and in situ hybridization (ISH). In addition, we examined the nuclear accumulation of Smad1, -2, -3, -5, and -8 proteins after intracerebroventricular injection of TGF-β1, activin A, or BMP6 with immunohistochemistry to investigate whether TGF-β, activin, and/or BMP activate Smads in the rat brain...
November 28, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29190740/correlation-of-serum-cytokines-chemokines-growth-factors-and-enzymes-with-periodontal-disease-parameters
#17
Jeneen Panezai, Ambereen Ghaffar, Mohammad Altamash, Karl-Gösta Sundqvist, Per-Erik Engström, Anders Larsson
BACKGROUND: Periodontal disease (PD) is characterized by inflammatory tissue destruction in tooth supporting apparatus. Many studies indicate that the underlying pathogenesis is in concordance with rheumatoid arthritis (RA) sharing immune-inflammatory events affect both diseases. The aim of this study was to investigate serum cytokines, chemokines, growth factors, enzymes and costimulatory proteins in association with periodontal conditions in PD and RA subjects. MATERIALS & METHODS: Periodontal examination was performed in RA (n = 38), PD (n = 38) and healthy subjects (n = 14)...
2017: PloS One
https://www.readbyqxmd.com/read/29189572/immunomodulation-of-human-mesenchymal-stem-stromal-cells-in-intervertebral-disc-degeneration-insights-from-a-proinflammatory-degenerative-ex-vivo-model
#18
Graciosa Q Teixeira, Catarina Leite Pereira, Joana R Ferreira, André F Maia, Maria Gomez-Lazaro, Mário A Barbosa, Cornelia Neidlinger-Wilke, Raquel M Goncalves
STUDY DESIGN: Ex vivo experimental study. OBJECTIVE: To investigate the effect of proinflammatory/degenerative intervertebral disc (IVD) microenvironment on the regenerative and immunomodulatory behavior of mesenchymal stem/stromal cells (MSCs), using an ex vivo model from bovine origin. SUMMARY OF BACKGROUND DATA: Low back pain (LBP) is a cause of disability worldwide, most frequently associated with IVD degeneration and inflammation, and characterized by increased levels of inflammatory mediators, often disregarded...
November 17, 2017: Spine
https://www.readbyqxmd.com/read/29187870/ectopic-expression-of-snail-and-twist-in-ph-leukemia-cells-upregulates-cd44-expression-and-alters-their-differentiation-potential
#19
Noa Kidan, Hazem Khamaisie, Nili Ruimi, Shay Roitman, Elizabeth Eshel, Najib Dally, Martin Ruthardt, Jamal Mahajna
Philadelphia chromosome-positive (Ph+) leukemia is characterized by reciprocal translocation between chromosomes 9 and 22. The resultant BCR/ABL fusion protein displays constitutive tyrosine kinase activity, leading to the induction of aberrant proliferation and neoplastic transformation. The bone marrow (BM) microenvironment is tumor-promoting, and contributes to disease recurrence in Ph+ leukemia. Activity in the BM microenvironment is mediated by several cellular compartments, extracellular matrix, various soluble factors including transforming growth factor beta 1 (TGF-β1), and the hypoxic conditions in the BM niche...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29187373/klotho-activin-a-in-kidney-injury-plasma-klotho-is-maintained-in-unilateral-obstruction-despite-no-upregulation-of-klotho-biosynthesis-in-contralateral-kidney
#20
Anders Nordholm, Maria L Mace, Eva Gravesen, Jacob Hofman-Bang, Marya Morevati, Klaus Olgaard, Ewa Lewin
In a new paradigm of etiology related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while ActivinA might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in obstructed kidney, untouched contralateral kidney and vasculature, which might be affected by secreted factors from the obstructed kidney, and compared to unilateral nephrectomized controls (UNX)...
November 29, 2017: American Journal of Physiology. Renal Physiology
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