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https://www.readbyqxmd.com/read/28898718/interleukin-17-regulates-shp-2-and-il-17ra-stat-3-dependent-cyr61-il-23-and-gm-csf-expression-and-rankl-mediated-osteoclastogenesis-by-fibroblast-like-synoviocytes-in-rheumatoid-arthritis
#1
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Interleukin (IL)-17 predominately produced by the Th17 cells, plays a crucial role in the fibroblast-like synoviocytes (FLS) mediated disease process of rheumatoid arthritis (RA). IL-17 exerts its pathogenic effects in RA-FLS by IL-17/IL-17RA/STAT-3 signaling. Recent studies have shown that RA-FLS produces SHP-2, Cyr61, IL-23, GM-CSF and RANKL which results in worsening of the disease. However, whether IL-17/IL-17RA/STAT-3 signaling regulates SHP-2, Cyr61, IL-23, GM-CSF and RANKL expressions in RA-FLS remains unknown...
September 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28834539/butyrate-stimulates-the-growth-of-human-intestinal-smooth-muscle-cells-by-activation-of-yes-associated-protein
#2
Li-Na Dai, Jun-Kai Yan, Yong-Tao Xiao, Jie Wen, Tian Zhang, Ke-Jun Zhou, Yang Wang, Wei Cai
Intestinal smooth muscle cells play a critical role in the remodeling of intestinal structure and functional adaptation after bowel resection. Recent studies have shown that supplementation of butyrate (Bu) contributes to the compensatory expansion of a muscular layer of the residual intestine in a rodent model of short-bowel syndrome (SBS). However, the underlying mechanism remains elusive. In this study, we found that the growth of human intestinal smooth muscle cells (HISMCs) was significantly stimulated by Bu via activation of Yes-Associated Protein (YAP)...
August 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28822004/in-vitro-validation-of-the-hippo-pathway-as-a-pharmacological-target-for-canine-mammary-gland-tumors
#3
Samantha Guillemette, Charlène Rico, Philippe Godin, Derek Boerboom, Marilène Paquet
Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Some clinical and molecular similarities between certain CMT subtypes and breast cancer make them a potential model for the study of the human disease. As misregulated Hippo signaling is thought to play an important role in breast cancer development and also occurs in CMTs, we sought to determine if Hippo represents a valid pharmacological target for the treatment of CMTs. Six CMT cell lines were assessed for their expression of the Hippo pathway effectors YAP and TAZ and for their sensitivity to verteporfin, an inhibitor of YAP-mediated transcriptional coactivation...
August 18, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28790340/verteporfin-inhibits-growth-of-human-glioma-in-vitro-without-light-activation
#4
Ahmad Al-Moujahed, Katarzyna Brodowska, Tomasz P Stryjewski, Nikolaos E Efstathiou, Ioannis Vasilikos, Joanna Cichy, Joan W Miller, Evangelos Gragoudas, Demetrios G Vavvas
Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19)...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28750181/sirt-1-regulates-tgf-%C3%AE-induced-dermal-fibroblast-migration-via-modulation-of-cyr61-expression
#5
Eun-Jeong Kwon, Eun-Jung Park, Hyeran Yu, Jung-Sik Huh, Jinseok Kim, Moon-Jae Cho
SIRT1 is a NAD-dependent protein deacetylase that participates in cellular regulation. The increased migration of fibroblasts is an important phenotype in fibroblast activation. The role of SIRT1 in cell migration remains controversial as to whether SIRT1 acts as an activator or suppressor of cell migration. Therefore, we have established the role of SIRT1 in the migration of human dermal fibroblasts and explored targets of SIRT1 during dermal fibroblast migration. SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation with TGF-β further induced their expression...
July 27, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28700567/recombinant-ccn1-prevents-hyperoxia-induced-lung-injury-in-neonatal-rats
#6
Ruben Vaidya, Ronald Zambrano, Julia K Hummler, Shihua Luo, Matthew R Duncan, Karen Young, Lester F Lau, Shu Wu
BACKGROUND: Cystein rich protein 61 (Cyr61/CCN1) is a member of the CCN family of matricellular proteins that plays an improtant role in tissue development and remodeling. However, the role of CCN1 in in the pathogensis of bronchopulmonary dysplasia (BPD) is unknown. Accordingly, we have investigated the effects of CCN1 on a hyperoxia-induced lung injury model in neonatal rats. METHODS: In experiment 1: newborn rats were randomized to room air (RA) or 85% oxygen (O2) for 7 or 14 days and we assessed the expression of CCN1...
July 12, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28694244/tumor-matrix-stiffness-promotes-metastatic-cancer-cell-interaction-with-the-endothelium
#7
Steven E Reid, Emily J Kay, Lisa J Neilson, Anne-Theres Henze, Jens Serneels, Ewan J McGhee, Sandeep Dhayade, Colin Nixon, John Bg Mackey, Alice Santi, Karthic Swaminathan, Dimitris Athineos, Vasileios Papalazarou, Francesca Patella, Álvaro Román-Fernández, Yasmin ElMaghloob, Juan Ramon Hernandez-Fernaud, Ralf H Adams, Shehab Ismail, David M Bryant, Manuel Salmeron-Sanchez, Laura M Machesky, Leo M Carlin, Karen Blyth, Massimiliano Mazzone, Sara Zanivan
Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction...
August 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28647210/high-expression-levels-of-cyr61-and-vegf-are-associated-with-poor-prognosis-in-osteosarcoma
#8
Yanming Liu, Feiyue Zhang, Zhaobo Zhang, Daoqing Wang, Baojuan Cui, Fanshuo Zeng, Laigang Huang, Qi Zhang, Qiangsan Sun
Cysteine Rich Angiogenic Inducer 61 (Cyr61) and Vascular Endothelial Growth Factor (VEGF) are signaling proteins involved in the regulation of tumor angiogenesis and progression. The purpose of this study was to investigate the clinicopathological and prognostic significance of Cyr61 and VEGF expressions in osteosarcoma. Immunohistochemical staining was performed to evaluate the expression of both the proteins in 84 osteosarcoma samples. Correlation between Cyr61/VEGF expressions and clinicopathological parameters was determined using Rank sum test and Spearman's rank correlation coefficient...
August 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28621618/placental-imprinting-variation-associated-with-assisted-reproductive-technologies-and-subfertility
#9
Julia F Litzky, Maya A Deyssenroth, Todd M Everson, David A Armstrong, Luca Lambertini, Jia Chen, Carmen J Marsit
Infertility affects one in 6 couples in developed nations, resulting in an increasing use of assisted reproductive technologies (ART). Both ART and subfertility appear to be linked to lower birth weight outcomes, setting infants up for poor long-term health. Prenatal growth is, in part, regulated via epigenetically-controlled imprinted genes in the placenta. Although differences in DNA methylation between ART and control infants have been found, it remains unclear whether these differences are due to the ART procedures or to the underlying parental subfertility and how these methylation differences affect imprinted gene expression...
June 16, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28608634/molecular-basis-for-the-recognition-of-ccn1-by-monoclonal-antibody-093g9
#10
Chen Zhong, Rongfen Huo, Kuan Hu, Jinlong Shen, Dangsheng Li, Ningli Li, Jianping Ding
CCN1, also named Cyr61 (cysteine-rich protein 61), is the first identified member of the CCN family that is composed of 6 secreted extracellular matrix-associated glycoproteins. CCN1 has been demonstrated to participate in pathogenesis of rheumatoid arthritis through various pathways. A monoclonal antibody, namely, 093G9, is effective to antagonize the effects of CCN1 and hence has potential therapeutic benefits against rheumatoid arthritis. Here, we show that the epitope recognized by 093G9 is mapped to residues 77 to 80 of CCN1, and a cyclic peptide encompassing residues 75 to 81 of CCN1 displays high binding affinity for 093G9...
June 13, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28602508/cyr61-ccn1-induces-ccl20-production-by-keratinocyte-via-activating-p38-and-jnk-ap-1-pathway-in-psoriasis
#11
Huidan Li, Haichuan Li, Rongfen Huo, Pinru Wu, Zhengyu Shen, Hui Xu, Baihua Shen, Ningli Li
BACKGROUND: Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) has recently been implicated in psoriasis pathogenesis by promoting keratinocyte activation. However, the mechanisms by which CCN1 enhances cutaneous inflammation are not fully understood. OBJECTIVE: In this study, we investigated the role of CCN1 on the expression of CCL20 in human keratinocyte. METHODS AND RESULTS: By double-label immunofluorescence staining, we first identified that the expression of CCN1 colocalized well with CCL20 production in the epidermis of psoriasis skin lesion...
June 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28548552/serum-cyr61-is-associated-with-disease-activity-in-graves-orbitopathy
#12
Young Jun Woo, Yuri Seo, Jin Joo Kim, Ji Won Kim, Yil Park, Jin Sook Yoon
PURPOSE: To investigate the clinical implications of cysteine-rich angiogenic inducer 61 (CYR61) in Graves' orbitopathy (GO). METHODS: Sera from 52 GO patients, 23 Graves' disease (GD) patients, and 20 healthy controls, and orbital fat tissue samples from 12 of 52 GO patients and 8 control subjects were included for analysis. Concentrations of CYR61 were measured from sera with an enzyme-linked immunosorbent assay, and CYR61 mRNA expression levels were evaluated from orbital fat tissue with polymerase chain reaction...
May 26, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28527710/ccn3-regulates-macrophage-foam-cell-formation-and-atherosclerosis
#13
Hong Shi, Chao Zhang, Vinay Pasupuleti, Xingjian Hu, Domenick A Prosdocimo, Wenconghui Wu, Yulan Qing, Shitong Wu, Haneen Mohammad, Stanton L Gerson, Bernard Perbal, Philip A Klenotic, Nianguo Dong, Zhiyong Lin
Recent studies implicate the Cyr61, CTGF, Nov (CCN) matricellular signaling protein family as emerging players in vascular biology, with NOV (alias CCN3) as an important regulator of vascular homeostasis. Herein, we examined the role of CCN3 in the pathogenesis of atherosclerosis. In response to a 15-week high-fat diet feeding, CCN3-deficient mice on the atherosclerosis-prone Apoe(-/-) background developed increased aortic lipid-rich plaques compared to control Apoe(-/-) mice, a result that was observed in the absence of alterations in plasma lipid content...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28523566/radial-glia-cells-control-angiogenesis-in-the-developing-cerebral-cortex-through-tgf-%C3%AE-1-signaling
#14
Michele Siqueira, Daniel Francis, Diego Gisbert, Flávia Carvalho Alcantara Gomes, Joice Stipursky
Neuroangiogenesis in the developing central nervous system is controlled by interactions between endothelial cells (ECs) and radial glia (RG) neural stem cells, although RG-derived molecules implicated in these events are not fully known. Here, we investigated the role of RG-secreted TGF-β1, in angiogenesis in the developing cerebral cortex. By isolation of murine microcapillary brain endothelial cells (MBECs), we demonstrate that conditioned medium from RG cultures (RG-CM) promoted MBEC migration and formation of vessel-like structures in vitro, in a TGF-β1-dependent manner...
May 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28512636/expression-of-yap-taz-in-keratocystic-odontogenic-tumors-and-its-possible-association-with-proliferative-behavior
#15
Qi-Wen Man, Yan-Qi Ma, Jin-Yuan Liu, Yi Zhao, Bing Liu, Yi-Fang Zhao
The aim of this study is to clarify whether YAP/TAZ is involved in the pathogenesis and proliferative growth of keratocystic odontogenic tumor (KCOT). The expression levels of YAP/TAZ and downstream proteins and genes in normal oral mucosa (OM) and KCOT were determined and compared by immunohistochemistry and real-time quantitative PCR. The results showed that the expression of YAP/TAZ and downstream proteins (Cyr61, CTGF) was significantly upregulated in KCOT with upregulation of Ki-67 compared to OM. Importantly, the mRNA levels of transcription factors (TEAD1, TEAD4, and RUNX2) and cell cycle related genes (CDK2, PCNA), which interact with the transcriptional coactivators YAP/TAZ, are also upregulated in the KCOT...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28487958/effects-of-taz-on-human-dental-pulp-stem-cell-proliferation-and-migration
#16
Songbo Tian, Xiaochao Tian, Yanping Liu, Fusheng Dong, Jie Wang, Xuqian Liu, Zhiyong Zhang, Huizhen Chen
Transcriptional coactivator with PDZ‑binding motif (TAZ) acts as the key downstream regulatory target in the Hippo signaling pathway. TAZ overexpression has been reported to promote cellular proliferation and induce epithelial‑mesenchymal transition in human mammary epithelial cells. However, the effects of TAZ in the regulation of human dental pulp stem cell (hDPSC) proliferation and migration, as well as the molecular mechanisms underlying its actions, remain to be elucidated. The present study demonstrated that TAZ was expressed in hDPSCs...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28483529/tead1-mediates-the-oncogenic-activities-of-hippo-yap1-signaling-in-osteosarcoma
#17
Jiwei Chai, Shijie Xu, Fengbo Guo
Hippo signaling pathway is an evolutionarily conserved developmental network that governs the downstream transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs that responsible for cell proliferation, apoptosis, and stem cell self renewal. Emerging evidence has shown the tumor suppressor properties of Hippo signaling. However, limited knowledge is available concerning the downstream transcription factors of Hippo pathway in osteosarcoma (OS). In this study, we demonstrated that TEAD1 was the major transcription factor of Hippo signaling pathway in OS...
May 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28469167/interplay-between-ccn1-and-wnt5a-in-endothelial-cells-and-pericytes-determines-the-angiogenic-outcome-in-a-model-of-ischemic-retinopathy
#18
Sangmi Lee, Menna Elaskandrany, Lester F Lau, Douglas Lazzaro, Maria B Grant, Brahim Chaqour
CYR61-CTGF-NOV (CCN)1 is a dynamically expressed extracellular matrix (ECM) protein with critical functions in cardiovascular development and tissue repair. Angiogenic endothelial cells (ECs) are a major cellular source of CCN1 which, once secreted, associates with the ECM and the cell surface and tightly controls the bidirectional flow of information between cells and the surrounding matrix. Endothelium-specific CCN1 deletion in mice using a cre/lox strategy induces EC hyperplasia and causes blood vessels to coalesce into large flat hyperplastic sinuses with no distinctive hierarchical organization...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28426731/effect-of-genetic-variation-in-microrna-binding-site-in-wnt1-inducible-signaling-pathway-protein-1-gene-on-oral-squamous-cell-carcinoma-susceptibility
#19
Hon-Kit Lau, Edie-Rosmin Wu, Mu-Kuan Chen, Ming-Ju Hsieh, Shun-Fa Yang, Lyu-Yao Wang, Ying-Erh Chou
BACKGROUND: Oral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%-2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1), a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and clinicopathologic characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/28384715/retinal-degeneration-triggers-the-activation-of-yap-tead-in-reactive-m%C3%A3-ller-cells
#20
Annaïg Hamon, Christel Masson, Juliette Bitard, Linn Gieser, Jérôme E Roger, Muriel Perron
Purpose: During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death. Methods: Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30...
April 1, 2017: Investigative Ophthalmology & Visual Science
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