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Pinru Wu, Gang Ma, Xianjin Zhu, Ting Gu, Jie Zhang, Yue Sun, Hui Xu, Rongfen Huo, Beiqing Wang, Baihua Shen, Xiangdong Chen, Ningli Li
PURPOSE: Interleukin-8 (IL-8) is an important factor in the pathogenesis of psoriasis vulgaris, which is characterized by proliferation of keratinocytes, neutrophil infiltration and angiogenesis. Cysteine-rich 61 (Cyr61/CCN1), a secreted extracellular matrix protein, is a novel proinflammatory factor. Whether Cyr61 is involved in the development of psoriasis vulgaris via IL-8 production remains unknown. In this study we explore the role of Cyr61 in IL-8 expression regulation in vivo and in vitro...
November 14, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Qunfeng Wu, Marda Jorgensen, Joanna Song, Junmei Zhou, Chen Liu, Liya Pi
Hepatic stem/progenitor cells (HPC) reside quiescently in normal biliary trees and are activated in the form of ductular reactions during severe liver damage when the replicative ability of hepatocytes is inhibited. HPC niches are full of profibrotic stimuli favoring scarring and hepatocarcinogenesis. The Cyr61/CTGF/NOV (CCN) protein family consists of six members, CCN1/CYR61, CCN2/CTGF, CCN3/NOV, CCN4/WISP1, CCN5/WISP2, and CCN6/WISP3, which function as extracellular signaling modulators to mediate cell-matrix interaction during angiogenesis, wound healing, fibrosis, and tumorigenesis...
2016: Gastroenterology Research and Practice
Feng Hao, Fuqiang Zhang, Daniel Dongwei Wu, Dong An, Jing Shi, Guohong Li, Xuemin Xu, Mei-Zhen Cui
Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation...
October 19, 2016: American Journal of Physiology. Cell Physiology
Priyanka Ghosh, Snigdha Banerjee, Gargi Maity, Archana De, Sushanta K Banerjee
In situ hybridization is an ideal tool for the detection and localization of mRNA expression of specific gene(s) in tissue sections and cell lines for prognosis, predictive markers, and highlighted potential therapeutic targets. Given the importance of CCN1 and CCN5 in breast and pancreatic cancer progression, these two secretory proteins could be novel therapeutic targets. Thus, evaluating the distribution of mRNA of these targets using in situ hybridization could be important preclinical tools. This chapter describes a detailed in situ hybridization technique for the detection of CCN1 and CCN5 in formalin-fixed, paraffin-embedded patient samples of breast and pancreatic cancers...
2017: Methods in Molecular Biology
Ricardo I Monzon, Ki-Hyun Kim, Lester F Lau
The embryonic lethality of mice with conventional global knockout of Ccn1 (Cyr61) precludes analysis of Ccn1 functions in late embryonic development or in adulthood. To circumvent this limitation, we have generated conditional knockout mice that allow cell type-specific deletion of Ccn1, and constructed an allelic series of Ccn1 knockin mice that express CCN1 defective for binding specific integrins in lieu of the wild type protein. Here we describe the construction of these mice and discuss how analysis of these animals can provide unique insights into Ccn1 functions mediated through specific integrin receptors...
2017: Methods in Molecular Biology
Xianjin Zhu, Yanfang Song, Conglian Wu, Chuxi Pan, Pingxia Lu, Meihua Wang, Peizheng Zheng, Rongfen Huo, Chenqing Zhang, Wanting Li, Yulin Lin, Yingping Cao, Ningli Li
Cyr61 (CCN1) is the product of a growth factor-inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients...
October 11, 2016: Scientific Reports
Javier A Menendez, Luciano Vellon, Ingrid Espinoza, Ruth Lupu
The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer cells with proliferative and survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up-regulated FASN protein expression and also significantly increased FASN gene promoter activity 2- to 3-fold, whereas deletion of the sterol response element-binding protein (SREBP) binding site in the FASN promoter completely abrogated CCN1-driven transcriptional activation...
2016: Oncoscience
Yu Di, Yiou Zhang, Linping Hui, Hongwei Yang, Yang Yang, Aiyuan Wang, Xiaolong Chen
Hypoxia is a key factor in the pathogenesis of angiogenesis, and cysteine‑rich 61 (CCN1), an angiogenic factor, is involved in the development of pathological angiogenesis. The aim of the present study was to investigate the mechanism of CCN1 RNA interference (RNAi)‑induced inhibition of hypoxia‑induced pathological angiogenesis in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions in vitro. The effects of inhibiting phosphoinositide 3‑kinase (PI3K)/Akt signaling using LY294002 were investigated in hypoxic HUVECs...
September 26, 2016: Molecular Medicine Reports
Jun Chen, Yang Liu, Qilin Sun, Beiqing Wang, Ningli Li, Xiangdong Chen
Cysteine-rich protein 61 (CCN1/CYR61) is an important marker of proliferation and metastasis in malignant melanoma, making it a potential target for melanoma treatment. In this study, we compared the expression of CRY61 in Chinese patients with malignant melanoma with its expression in patients with other skin tumors or with no skin pathological conditions. We examined the effects of anti-human CYR61 monoclonal antibody on proliferation and evaluated the changes in CYR61 expression and cell proliferation in response to treatment with either epirubicin or interferon (IFN)-α...
September 23, 2016: Oncology Reports
Annick Perbal, Bernard Perbal
The CCN family of proteins is composed of six members, which are now well recognized as major players in fundamental biological processes. The first three CCN proteins discovered were designated CYR61, CTGF, and NOV because of the context in which they were identified. Both CYR61 and CTGF were discovered in normal cells, whereas NOV was identified in tumors. Soon after their discovery, it was established that they shared important and unique structural features and distinct biological properties. Based on these structural considerations, the three proteins were proposed to belong to a family that was designated CCN by P...
September 2016: Journal of Cell Communication and Signaling
Caroline Barranco
No abstract text is available yet for this article.
October 2016: Nature Reviews. Rheumatology
Celina G Kleer
The tumor microenvironment has a powerful effect on the development and progression of human breast cancer, which may be used therapeutically. Despite efforts to understand the complex role of the tumor microenvironment in breast cancer development, the specific players and their contributions to tumorigenesis need further investigation. The CCN family of matricellular proteins comprises six members (CCN1-6; CYR61, CTGF, NOV, WISP1-3) with central roles in development, inflammation, and tissue repair. CCN proteins also exert functions during pathological processes including fibrosis and cancer by regulating extracellular signals in the cellular environment...
September 2016: Journal of Cell Communication and Signaling
Herman Yeger, Bernard Perbal
The CCN family of proteins consisting of CCN1 (Cyr61), CCN2 (CTGF), CCN3 (NOV), CCN4 (WISP-1), CCN5 (WISP-2) and CCN6 (WISP-3) are considered matricellular proteins operating essentially in the extracellular microenvironment between cells. Evidence has also been gradually building since their first discovery of additional intracellular roles although the major activity is triggered at the cell membrane. The proteins consist of 4 motifs, a signal peptide (for secretion} followed consecutively by the IGFBP, VWC, TSP1 and CT (C-terminal cysteine knot domain) motifs, which signify their potential binding partners and functional connections to a variety of key regulators of physiological processes...
September 2016: Journal of Cell Communication and Signaling
Beat A Imhof, Stephane Jemelin, Romain Ballet, Christian Vesin, Marco Schapira, Melis Karaca, Yalin Emre
Inflammation is characterized by the recruitment of leukocytes from the bloodstream. The rapid arrival of neutrophils is followed by a wave of inflammatory lymphocyte antigen 6 complex (Ly6C)-positive monocytes. In contrast Ly6C(low) monocytes survey the endothelium in the steady state, but their role in inflammation is still unclear. Here, using confocal intravital microscopy, we show that upon Toll-like receptor 7/8 (TLR7/8)-mediated inflammation of mesenteric veins, platelet activation drives the rapid mobilization of Ly6C(low) monocytes to the luminal side of the endothelium...
August 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Georgina S Butler, Andrea R Connor, Nor Eddine Sounni, Ulrich Eckhard, Charlotte J Morrison, Agnès Noël, Christopher M Overall
: Members of the CCN family of matricellular proteins are cytokines linking cells to the extracellular matrix. We report that CCN3 (Nov) and CCN5 (WISP2) are novel substrates of MMP14 (membrane-type 1-matrix metalloproteinase, MT1-MMP) that we identified using MMP14 "inactive catalytic domain capture" (ICDC) as a yeast two-hybrid protease substrate trapping platform in parallel with degradomics mass spectrometry screens for MMP14 substrates. CCN3 and CCN5, previously unknown substrates of MMPs, were biochemically validated as substrates of MMP14 and other MMPs in vitro-CCN5 was processed in the variable region by MMP14 and MMP2, as well as by MMP1, 3, 7, 8, 9 and 15...
July 25, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Cheng-Yu Chen, Chen-Ming Su, Chin-Jung Hsu, Chien-Chung Huang, Shih-Wei Wang, Shih-Chia Liu, Wei-Cheng Chen, Lih-Jyh Fuh, Chih-Hsin Tang
Angiogenesis is the formation of new capillaries from pre-existing vasculature. The perpetuation of angiogenesis plays a critical role in the pathogenesis of various disease states including rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61 or CCN1) is an important proinflammatory cytokine in RA. Here, we investigated the role of CCN1 in angiogenesis associated with vascular endothelial growth factor (VEGF) production and osteoblasts. We found higher expression of CCN1 and VEGF in synovial fluid from RA patients compared with healthy controls...
July 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Tao Xu, Ying-Hua He, Ming-Quan Wang, Hong-Wei Yao, Ming-Ming Ni, Lei Zhang, Xiao-Ming Meng, Cheng Huang, Yun-Xuan Ge, Jun Li
Cysteine-rich protein 61 (Cyr61)/CCN1, a product of an immediate early gene, can directly accommodate cell adhesion and migratory processes whilst simultaneously regulating the production of other cytokines and chemokines through paracrine and autocrine feedback loops. This intricate functionality of Cyr61 indicate its important role in targeting components of the infectious or chronic inflammatory disease processes including rheumatoid arthritis (RA). Recent work has focused on the role of Cyr61 in RA. For example, Cyr61 induced proIL-1β production in FLS via the AKT-dependent NF-κB signaling pathway...
October 30, 2016: Gene
Yan Wang, Mengchun Wang
BACKGROUND: This study aimed to evaluate the clinical significance of cysteine-rich 61 (Cyr-61/CCN1) and cyclooxygenase-2 (COX-2), and further explored their combined prognostic significance in gastric cancer. METHODS: This retrospective study examined the expressions of Cyr-61 and COX-2 in 82 surgically removed gastric cancer specimens and 43 non-tumor gastric mucosa specimens by immunohistochemical staining to identify the abnormal expression of Cyr-61 or COX-2 in gastric cancer...
2016: BMC Gastroenterology
Erawan Borkham-Kamphorst, Bettina Therese Steffen, Eddy Van de Leur, Lidia Tihaa, Ute Haas, Marius M Woitok, Steffen K Meurer, Ralf Weiskirchen
The endoplasmic reticulum (ER) is primarily recognized as the site of synthesis and folding of secreted membrane-bound and certain organelle-targeted proteins. Optimum protein folding requires several factors, including ATP, Ca(2+) and an oxidizing environment to allow disulphide-bond formation. ER is highly sensitive to stress that perturb cellular energy levels, the redox state or the Ca(2+) concentration. Such stresses reduce the protein folding capacity of the ER, resulting in the accumulation and aggregation of unfolded proteins, a condition referred to as unfolded protein response (UPR)...
November 2016: Biochimica et Biophysica Acta
Philip A Klenotic, Chao Zhang, Zhiyong Lin
The CCN family of proteins consists of 6 members (CCN1-CCN6) that share conserved functional domains. These matricellular proteins interact with growth factors, extracellular matrix (ECM) proteins, cell surface integrins and other receptors to promote ECM-intracellular signaling. This signaling leads to propagation of a variety of cellular actions, including adhesion, invasion, migration and proliferation within several cell types, including epithelial, endothelial and smooth muscle cells. Though CCNs share significant homology, the function of each is unique due to distinct and cell specific expression patterns...
May 30, 2016: Journal of Cell Communication and Signaling
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