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Zhongyi Xu, Li Chen, Min Jiang, Qianqian Wang, Chengfeng Zhang, Leihong Flora Xiang
Fibroblast-derived melanogenic paracrine mediators are known to play a role in melanogenesis. To investigate the effect of CCN1 (also called CYR61, cysteine-rich 61) on melanogenesis, normal human epidermal melanocytes (NHEMs) were treated with recombinant CCN1 protein. Our findings reveal that CCN1 activates melanogenesis through promoting melanosome maturation and upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1) and tyrosinase via integrin α6β1, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways...
March 3, 2018: Journal of Investigative Dermatology
Ming Gao, Minjun Chen, Changying Li, Ming Xu, Yun Liu, Min Cong, Nan Sang, Sijin Liu
Metallothioneins (MTs) are known to protect cells against oxidative stress, especially providing protection against cadmium (Cd) toxicity in hepatocytes. There are various gene variants and pseudogenes for MTs; however, there is little understanding on the functions of those non-coding MT members that are known to be expressed as long non-coding RNAs (lncRNAs) nowadays. Different from most protein-coding MT members, MT1DP was here found that remarkably induced to provoke cytotoxicity in hepatocytes in response to Cd treatment...
2018: Cell Discovery
Tarunkumar Hemraj Madne, Mark Edward Carl Dockrell
Growth factors like TGFβ and CTGF (CCN2) plays a vital role in various cellular functions. TGFβ and CTGF are overexpressed in renal fibrosis. CTGF act as profibrotic stimuli to TGFβ. CCN3 is a member of CCN family which also comprises CCN1 (CYR61), CCN2 (CTGF), CCN4 (WISP-1), CCN5 (WISP-2) and CCN6 (WISP-3). CCN3 has been shown to antagonise CTGF. In this study, we investigated the role of CCN3 in TGFβ1-mediated signalling in human podocytes culture. This study describes the novel function of CCN3 in regulation of TGFβ1 mediated non-canonical Smad signalling in human podocytes culture...
February 28, 2018: Cellular and Molecular Biology
Gargi Maity, Inamul Haque, Arnab Ghosh, Gopal Dhar, Vijayalaxmi G Gupta, Sandipto Sarkar, Imaan Azeem, Douglas McGregor, Abhishek Choudhary, Donald R Campbell, Suman Kambhampati, Sushanta K Banerjee, Snigdha Banerjee
Myc-associated zinc-finger protein (MAZ) is a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression is associated with the progression of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of action of MAZ in PDAC progression is largely unknown. Here, we present evidence that MAZ mRNA expression and protein levels are increased in human PDAC cell lines, tissue samples, a subcutaneous tumor xenograft in a nude mouse model, and spontaneous cancer in the genetically engineered PDAC mouse model...
February 6, 2018: Journal of Biological Chemistry
Stephen M Twigg
Across the years the CCNs have been increasingly implicated in the development of obesity, diabetes and its complications. Evidence for this is currently derived from their dysregulation in key metabolic pathological states in humans, animal and in vitro models, and also pre-clinical effects of their bioactivities. CCN2 is the best studied in this disease process and the other CCNs are yet to be better defined. Key steps where CCNs may play a pathogenic metabolic role include: (i) obesity and insulin resistance, where CCN2 inhibits fat cell differentiation in vitro and CCN3 may induce obesity and insulin resistance; (ii) elevated blood glucose levels to diabetes mellitus onset, where CCN2 may contribute to pancreatic beta cell and islet function; and (iii) in diabetes complications, such as nephropathy, retinopathy, liver disease (NAFLD/NASH), CVD and diabetes with heart failure...
February 6, 2018: Journal of Cell Communication and Signaling
Fan E Mo, Pei-Ling Hsu
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Ki-Hyun Kim, Jong Hoon Won, Naiyuan Cheng, Lester F Lau
The expression of Ccn1 (Cyr61) is essential for cardiovascular development during embryogenesis, whereas in adulthood it is associated with inflammation, wound healing, injury repair, and related pathologies including fibrosis and cancer. Recent studies have found that CCN1 plays a critical role in promoting wound healing and tissue repair. Mechanistically, CCN1 functions through direct interaction with specific integrin receptors expressed in various cell types in the wound tissue microenvironment to coordinate diverse cellular functions for repair...
January 22, 2018: Journal of Cell Communication and Signaling
Gexin Zhao, Bau-Lin Huang, Diana Rigueur, Weiguang Wang, Chimay Bhoot, Kemberly R Charles, Jongseung Baek, Subburaman Mohan, Jie Jiang, Karen M Lyons
CYR61/CCN1 is a matricellular protein that resides in the extracellular matrix, but serves regulatory rather than structural roles. CYR61/CCN1 is found in mineralized tissues and has been shown to influence bone healing in vivo and osteogenic differentiation in vitro. In this study we generated Cyr61 bone specific knockout mice to examine the physiological role of CYR61/CCN1 in bone development and maintenance in vivo. Extensive analysis of Cyr61 conditional knockout mice showed a significant decrease in both trabecular and cortical bone mass as compared to WT littermate...
January 19, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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...
March 2018: International Journal of Molecular Medicine
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...
June 2018: Journal of Cellular Physiology
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
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
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...
January 2018: Molecular Medicine Reports
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
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...
December 1, 2017: Experimental Cell Research
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
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
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
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
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
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