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https://www.readbyqxmd.com/read/29286082/ccn1-cyr61-enhances-the-function-of-hepatic-stellate-cells-in-promoting-the-progression-of-hepatocellular-carcinoma
#1
Zhi-Qiang Li, Wei-Ru Wu, Chen Zhao, Chen Zhao, Xiao-Li Zhang, Zhong Yang, Jing Pan, Wei-Ke Si
Hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)‑producing cells in liver fibrosis. Activated HSCs stimulate the proliferation and migration of hepatocellular carcinoma (HCC) cells. Cysteine‑rich 61 (CCN1/Cyr61) is an ECM protein. Our previous studies demonstrated that the expression of CCN1 was significantly higher in benign hepatic cirrhosis tissue and cancer‑adjacent hepatic cirrhosis tissues. CCN1 is a target gene of β‑catenin in HCC and promotes the proliferation of HCC cells...
December 29, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29219182/the-emerging-role-of-hippo-signaling-pathway-in-regulating-osteoclast-formation
#2
REVIEW
Wanlei Yang, Weiqi Han, An Qin, Ziyi Wang, Jiake Xu, Yu Qian
A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29209654/tumor-stiffness-extends-its-grip-on-the-metastatic-microenvironment
#3
Steven E Reid, Sara Zanivan
The increased stiffness of a tumor triggers a multitude of responses that aid cancer cell dissemination. Stiffness-induced expression of CCN1 mediates autocrine signaling in the endothelium to upregulate N-Cadherin levels. This permits more stable interactions with cancer cells and increases their ability to spread into the circulation.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29155984/cysteine-rich-angiogenic-inducer-61-cyr61-a-novel-soluble-biomarker-of-acute-myocardial-injury-improves-risk-stratification-after-acute-coronary-syndromes
#4
Roland Klingenberg, Soheila Aghlmandi, Christoph Liebetrau, Lorenz Räber, Baris Gencer, David Nanchen, David Carballo, Alexander Akhmedov, Fabrizio Montecucco, Stefan Zoller, Chad Brokopp, Dik Heg, Peter Jüni, Helena Marti Soler, Pedro-Manuel Marques-Vidal, Peter Vollenweider, Oliver Dörr, Nicolas Rodondi, François Mach, Stephan Windecker, Ulf Landmesser, Arnold von Eckardstein, Christian W Hamm, Christian M Matter, Thomas F Lüscher
Aims: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. Methods and results: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls...
November 16, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29115499/biological-functions-and-role-of-ccn1-cyr61-in-embryogenesis-and-tumorigenesis-in-the-female-reproductive-system-review
#5
Rui Yang, Ying Chen, Daozhen Chen
Cysteine‑rich angiogenic inducer 61 (CCN1/Cyr61) is a prompt response transcription product activated by growth factors. As a member of the CCN family, it mediates cell survival, proliferation, differentiation, migration, adhesion and synthesis of the extracellular matrix by binding directly to the integrins and heparin sulfate proteoglycans or activating multiple signaling transduction pathways. It has previously been demonstrated that CCN1/Cyr61 exhibits an important role in the female reproductive system during embryogenesis and tumorigenesis...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29089076/-screening-of-key-molecules-of-hab18g-cd147-signal-transduction-pathway-in-human-hepatoma-cells
#6
Hongwei Zhou, Yibing Yao, Yaojie Liang, Zhihong Wang, Xiaoyan Zhou, Weiping Guo, Xiangmin Yang, Jianli Jiang, Junzhong Sun, Zhinan Chen
Objective To screen the differentially expressed key molecules of HAb18G/CD147 signal transduction pathway in human hepatoma cells. Methods The total RNA was extracted from SMMC-7721 and T7721 cells, which were stably transfected and overexpressed HAb18G/CD147, and then detected by signal transduction-related microarray to identify differentially expressed key molecules. Results The microarray data indicated that there were 13 differentially expressed genes between T7721 and SMMC-7721 cells. In T7721 cell line which overexpressed HAb18G/CD147, the down-regulated genes included bone morphogenetic protein-2 (BMP-2), BMP-5, endothelin-1 (ET-1), Wnt1-induced signaling proteins-2/CCN5 (WISP-2), cysteine-rich 61/CCN1 (Cyr61), prostate stem cell antigen (PSCA), and the up-regulated genes included interleukin-10 receptor α (IL-10Rα), IL-6, IL-8, CXCL2, mitochondrial superoxide dismutase 2 (SOD2), B factor and βig-h3...
September 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29055676/ccn1-sensitizes-esophageal-cancer-cells-to-trail-mediated-apoptosis
#7
Tong Dang, Cristina Modak, Xiemei Meng, Jinbao Wu, Reinier Narvaez, Jianyuan Chai
TRAIL is one of the best anti-cancer molecules in our body. It kills a variety of cancer cells that are resistant to conventional chemotherapy, without causing much negative impact on normal cells, because its death receptors are almost exclusively found on cancer cells. However, some cancer cells are not sensitive to TRAIL treatment, even though they express its death receptors. A second molecule is needed to help TRAIL to complete its mission. Finding such molecules now becomes a top priority in cancer research...
October 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29049376/antioxidants-and-nox1-nox4-inhibition-blocks-tgf%C3%AE-1-induced-ccn2-and-%C3%AE-sma-expression-in-dermal-and-gingival-fibroblasts
#8
Hannah Murphy-Marshman, Katherine Quensel, Xu Shi-Wen, Rebecca Barnfield, Jacalyn Kelly, Alex Peidl, Richard J Stratton, Andrew Leask
TGFbeta induces fibrogenic responses in fibroblasts. Reactive oxygen species (ROS)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) may contribute to fibrogenic responses. Here, we examine if the antioxidant N-acetylcysteine (NAC), the NOX inhibitor diphenyleneiodonium (DPI) and the selective NOX1/NOX4 inhibitor GKT-137831 impairs the ability of TGFbeta to induce profibrotic gene expression in human gingival (HGF) and dermal (HDF) fibroblasts. We also assess if GKT-137831 can block the persistent fibrotic phenotype of lesional scleroderma (SSc) fibroblasts...
2017: PloS One
https://www.readbyqxmd.com/read/28806967/microrna-181c-inhibits-cigarette-smoke-induced-chronic-obstructive-pulmonary-disease-by-regulating-ccn1-expression
#9
Yong Du, Yi Ding, Xuru Chen, Zhoufang Mei, Heyuan Ding, Yi Wu, Zhijun Jie
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an obstinate pulmonary disease, causing irreversible alveoli collapse and increasing the risk for cardiovascular disease. Accumulating evidence has shown that the dysregulation of miRNAs is crucially involved in the pathogenesis and development of COPD. However, the effects and role of microRNA-181c (miR-181c) have not been investigated in a murine model of COPD. METHODS: miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of CS exposure, and primary human bronchial epithelial cells (HBECs) by qRT-PCR...
August 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28777871/the-functional-characteristics-ccni-modulation-of-myeloid-derived-suppressor-cells-in-liver-inflammation
#10
Haiyan Zhang, Min Lian, Jun Zhang, Zhaolian Bian, Ruqi Tang, Qi Miao, Yanshen Peng, Jingyuan Fang, Zhengrui You, Pietro Invernizzi, Qixia Wang, M Eric Gershwin, Xiong Ma
There is increasing awareness of the immunologic roles of liver mononuclear populations including myeloid-derived suppressor cells (MDSCs). We took advantage of a large well defined cohort of 148 patients with liver inflammation and 45 health controls to focus on the qualitative and quantitative characteristics of MDSCs. We investigated the frequency, phenotype and functional capacities of MDSCs using peripheral blood MDSCs in a cohort of 55 patients with PBC, 40 with AIH, 39 with CHB, 14 with NAFLD and 45 healthy controls, and thereafter a liver targeted determination in 27 PBC, 27 AIH, 20 CHB, 14 NAFLD and 6 controls...
August 4, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28712304/regulation-of-cellular-redox-signaling-by-matricellular-proteins-in-vascular-biology-immunology-and-cancer
#11
David D Roberts, Sukhbir Kaur, Jeffrey S Isenberg
SIGNIFICANCE: In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H2S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer...
October 20, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28700567/recombinant-ccn1-prevents-hyperoxia-induced-lung-injury-in-neonatal-rats
#12
Ruben Vaidya, Ronald Zambrano, Julia K Hummler, Shihua Luo, Matthew R Duncan, Karen Young, Lester F Lau, Shu Wu
BackgroundCystein-rich protein 61 (Cyr61/CCN1) is a member of the CCN family of matricellular proteins that has an important role in tissue development and remodeling. However, the role of CCN1 in the pathogenesis of bronchopulmonary dysplasia (BPD) is unknown. Accordingly, we have investigated the effects of CCN1 on a hyperoxia-induced lung injury model in neonatal rats.MethodsIn 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...
November 2017: Pediatric Research
https://www.readbyqxmd.com/read/28694244/tumor-matrix-stiffness-promotes-metastatic-cancer-cell-interaction-with-the-endothelium
#13
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/28638955/lipopolysaccharide-induced-ccn1-production-enhances-interleukin-6-secretion-in-bronchial-epithelial-cells
#14
Lin Shi, Nian Dong, Dongxiang Ji, Xiaomin Huang, Zhaojian Ying, Xiangdong Wang, Chengshui Chen
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical complication caused by primary or secondary lung injury, as well as by systemic inflammation. Researches regarding molecular pathophysiology of ALI/ARDS are immerging with an ultimate aim towards developing prognostic molecular biomarkers and molecule-based therapy. However, the molecular mechanisms concerning ALI/ARDS are still not completely understood. The purpose of the present study was to identify a crucial role of CCN1 in inflammatory microenvironment during ALI/ARDS and focus on a potential communication between CCN1 and interleukin-6 (IL-6) in the airway epithelial cells...
June 21, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28608634/molecular-basis-for-the-recognition-of-ccn1-by-monoclonal-antibody-093g9
#15
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
#16
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...
October 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28530164/biocompatibility-of-intensified-decellularized-equine-carotid-arteries-in-a-rat-subcutaneous-implantation-model-and-in-a-human-in-vitro-model
#17
Niklas Jeinsen, Lavinia Mägel, Danny Jonigk, Melanie Klingenberg, Axel Haverich, Mathias Wilhelmi, Ulrike Böer
Limited biocompatibility of decellularized scaffolds is an ongoing challenge in tissue engineering. We recently demonstrated that intensified detergent-based decellularization of equine carotid artery (dEACintens) removed residual cellular molecules from the scaffold more efficiently than a conventional decellularization (dEACcon), although this approach did not eliminate its immunogenicity entirely. CCN1 has been shown to improve biocompatibility of dEACcon in a sheep model. In this study, we tested the biocompatibility of dEACintens and dEACcon with or without CCN1 coating after subcutaneous implantation in rats for up to 12 weeks...
June 29, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28496027/expression-profile-of-matricellular-proteins-in-hypertrophied-right-ventricle-of-monocrotaline-induced-pulmonary-hypertensive-rats
#18
Keisuke Imoto, Muneyoshi Okada, Hideyuki Yamawaki
Matricellular proteins, a non-structural extracellular matrix (ECM) component, bind to and modulate various molecules including growth factor, cytokine, protease, other ECM components and cell membrane receptors. While most matricellular proteins are hardly expressed in normal adult tissue, they are re-expressed in heart tissue during cardiac diseases. The present study aimed to clarify the mRNA expression profile of matricellular proteins [secreted protein acidic and rich in cysteine: SPARC, hevin, thrombospondin (TSP)-1, -2 and -4, CCN1 and 5, tenascin (Tn) C and N, periostin and osteopontin (OPN)] in hypertrophied right ventricle (RV) of monocrotaline (MCT)-induced pulmonary hypertensive rats...
June 29, 2017: Journal of Veterinary Medical Science
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
#19
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/28460443/sphingosine-1-phosphate-promotes-ovarian-cancer-cell-proliferation-by-disrupting-hippo-signaling
#20
Qianlan Fan, Yuan Cheng, Hsun-Ming Chang, Masashi Deguchi, Aaron J Hsueh, Peter C K Leung
Epithelial ovarian carcinomas account for more than 90% of human ovarian cancers and have become the primary cause of death for gynecological malignancies. Unlimited cell proliferation and resistance to cell apoptosis contribute to the development of ovarian cancers. However, the underlying mechanisms involved in these processes in epithelial ovarian carcinomas are yet poorly understood. In the present study, we examined the Hippo signaling gene expression and investigated the effects of Sphingosine 1-phosphate (S1P) on cell proliferation and the underlying mechanisms in human ovarian cancer cell lines, OVCAR3 and SKOV3...
April 18, 2017: Oncotarget
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