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Jun Li, Xiangyu Gao, Ke Ji, Andrew J Sanders, Zhongtao Zhang, Wen G Jiang, Jiafu Ji, Lin Ye
CCN is an acronym for cysteine-rich protein 61 (CYR61), connective tissue growth factor (CTGF) and nephroblastoma overexpressed (NOV). Aberrations of certain CCN members including CYR61, CTGF, Wnt1-inducible signalling pathway protein (WISP)-1 and -3 have been reported in gastric cancer. The present study aimed to examine the clinical relevance of NOV along with CYR61 and CTGF in gastric cancer by analysing their transcript levels. CYR61, CTGF and NOV transcript expression in 324 gastric cancer samples with paired adjacent normal gastric tissues were determined using real-time quantitative PCR and the results were statistically analysed against patient clinicopathological data using SPSS software...
September 8, 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
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
Yuan-Liang Xue, Xiang-Qi Meng, Long-Jun Ma, Zhen Yuan
Plumbagin, a naphthoquinone constituent of Plumbago zeylanica L. (Plumbaginaceae) is widely used in traditional Chinese medicine as an antifungal, antibacterial and anti-inflammatory agent. Plumbagin is known to exhibit proapoptotic, antiangiogenic and antimetastatic effects in cancer cells. The transcriptional co-factor four and a half LIM domains 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of gene expression, signal transduction and cell proliferation and differentiation, and also acts as a tumor suppressor or oncoprotein depending on the tissue microenvironment...
August 2016: Oncology Letters
Helen Williams, Carina A E Mill, Bethan A Monk, Sarah Hulin-Curtis, Jason L Johnson, Sarah J George
OBJECTIVE: Increased vascular smooth muscle cell (VSMC) migration leads to intimal thickening which acts as a soil for atherosclersosis, as well as causing coronary artery restenosis after stenting and vein graft failure. Investigating factors involved in VSMC migration may enable us to reduce intimal thickening and improve patient outcomes. In this study, we determined whether Wnt proteins regulate VSMC migration and thereby intimal thickening. APPROACH AND RESULTS: Wnt2 mRNA and protein expression were specifically increased in migrating mouse aortic VSMCs...
July 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Ching-Chia Lin, Po-Chun Chen, Ming-Yu Lein, Ching-Wen Tsao, Chiu-Chen Huang, Shih-Wei Wang, Chih-Hsin Tang, Kwong-Chung Tung
Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by a poor prognosis and a low survival rate. Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis and is correlated with cancer metastasis. WNT1-inducible signaling pathway protein-1 (WISP)-1/CCN4 is an extracellular matrix-related protein that belongs to the CCN family and stimulates many biological functions. Our previous studies showed that WISP-1 plays an important role in OSCC migration and angiogenesis...
March 1, 2016: Oncotarget
Yunhua Xu, Shun Lu
OBJECT: The aim of this study was to explore the role of WNT1-inducible-signaling Pathway Protein 1 (WISP-1) in etoposide resistance in lung adenocarcinoma A549 cells. METHODS: WISP-1 overexpression A549 lung adenocarcinoma cell was established. After exposure to ultraviolet (UV) and etoposide, cell viability and apoptosis were evaluated. Moreover, western-blot was employed to examine the expression of apoptotic pathway proteins. In addition, a nude mice tumor model was established to examine the effect of WISP-1 overexpression in vivo and TUNEL staining was used to assess cell apoptosis of tumor tissue...
2015: International Journal of Clinical and Experimental Medicine
Li Li, Rakeshwar S Guleria, Suresh Thakur, Cheng-Lin Zhang, Jing Pan, Kenneth M Baker, Sudhiranjan Gupta
Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. However, the role of Tβ4 in cardiomyocyte hypertrophy is currently unknown. The purpose of this study was to determine the cardio-protective effect of Tβ4 in angiotensin II (Ang II)-induced cardiomyocyte growth. Neonatal rat ventricular cardiomyocytes (NRVM) were pretreated with Tβ4 followed by Ang II stimulation. Cell size, hypertrophy marker gene expression and Wnt signaling components, β-catenin, and Wnt-induced secreted protein-1 (WISP-1) were evaluated by quantitative real-time PCR, Western blotting and fluorescent microscopy...
August 2016: Journal of Cellular Physiology
Yuya Yoshioka, Mitsuaki Ono, Azusa Maeda, Tina M Kilts, Emilio Satoshi Hara, Hany Khattab, Junji Ueda, Eriko Aoyama, Toshitaka Oohashi, Masaharu Takigawa, Marian F Young, Takuo Kuboki
The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs...
February 2016: Bone
Jian-Yu Yang, Min-Wei Yang, Yan-Miao Huo, Wei Liu, De-Jun Liu, Jiao Li, Jun-Feng Zhang, Rong Hua, Yong-Wei Sun
WNT1 inducible signaling pathway protein 1 (WISP-1) is a member of the CCN family of growth factors and reported to possess an important role in tumorigenesis by triggering downstream events via integrin signaling. However, the exact role of WISP-1 in cancer remains unclear. In this study, we examined the expression pattern of WISP-1 at both mRNA and protein levels and evaluated the prognostic value of WISP-1 in pancreatic ductal adenocarcinoma (PDA). Expression of WISP-1 at mRNA level was upregulated in 17/24 tumor tissues compared to the matched adjacent non-tumor tissues and the result was confirmed by western blotting at protein level...
2015: American Journal of Translational Research
Jian Ge, Xiao-Hua Zhang, Fang Wang, Yu Wang, Qing-Yan Li, Wei Tao, Guo-Hua Ren
OBJECTIVE: To study the inhibition effect of siRNA on the expression of Wisp-1 gene in Hca-F of mouse hepatocellular carcinoma cells strain and also its effect on the proliferation, migration and adhesion of hepatocellular carcinoma cells. METHODS: Three expression vectors of siRNA were constructed. Lipo2000 was employed to transfect Hca-F cells and Western blot was used to detect the inhibition effect of siRNA on the expression of Wisp-1 gene. Afterward, CCK8 was adopted to detect the effect of Wisp-1 siRNA on the proliferation of Hca-F cells; Annexin V-FITC/PI double staining flow cytometry was used to detect the effect of Wisp-1 siRNA on the apoptosis of Hca-F cells; Transwell was used to detect the effect of Wisp-1 siRNA on the migration of Hca-F cells...
October 2015: Asian Pacific Journal of Tropical Medicine
Xinjun Zhao, Yue Hua, Hongmei Chen, Haiyu Yang, Tao Zhang, Guiqiong Huang, Huijie Fan, Zhangbin Tan, Xiaofang Huang, Bin Liu, Yingchun Zhou
BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) has a protective effect on ischemic heart disease. Here, we examined the protective effects of ALDH2 on cardiac fibrosis through modulation of the Wnt/β-catenin signaling pathway in a rat model of myocardial infarction (MI). METHODS: Wistar rats were divided into the sham (control), MI (model), and ALDH2 activator (Alda-1) groups. After 10 days of treatment, the left ventricular (LV) remodeling parameters of each animal were evaluated by echocardiography...
2015: Therapeutics and Clinical Risk Management
Javier Fernández-Torres, Cristina Hernández-Díaz, Rolando Espinosa-Morales, Javier Camacho-Galindo, Norma del Carmen Galindo-Sevilla, Ámbar López-Macay, Yessica Zamudio-Cuevas, Karina Martínez-Flores, Mónica Guadalupe Santamaría-Olmedo, Carlos Pineda, Julio Granados, Gabriela Angélica Martínez-Nava, Marwin Gutiérrez, Alberto G López-Reyes
BACKGROUND: Osteoarthritis (OA) is a multifactorial degenerative condition of the whole joint with a complex pathogenesis whose development and progression is significantly mediated by interactions between the joint cartilage and articular tissues, particularly, proinflammatory mediators and oxidative stress, which results in cartilage deterioration and subchondral bone destruction. HIF-1 alpha regulates oxygen homeostasis in hypoxic tissues such as joint cartilage; efficiency of transcriptional activity of the HIF1A gene is strongly influenced by the presence of polymorphic variants...
2015: BMC Musculoskeletal Disorders
Xiaofei Li, Yongxin Chen, Weiwei Ye, Xingfei Tao, Jinhong Zhu, Shuang Wu, Lianqing Lou
INTRODUCTION: CCN4, also termed WNT-inducible signaling pathway protein-1 (WISP-1), has important roles in inflammation and tissue injury. This study aimed to investigate the effect of CCN4 inhibition using monoclonal anti-CCN4 antibody (CCN4mAb) on the liver injury and fibrosis in a mouse model of liver fibrosis. MATERIAL AND METHODS: The mouse liver fibrosis model was induced by carbon tetrachloride (CCl4). Mice received vehicle (saline/olive oil) by subcutaneous injection, CCl4 by subcutaneous injection or CCl4 (subcutaneous) plus CCN4mAb by subcutaneous injection...
June 19, 2015: Archives of Medical Science: AMS
Chunyang Zhang, Yan Zhu, Yan Zhang, Lianru Gao, Ningkun Zhang, Huasong Feng
Radiation-induced lung injury (RILI) limits the benefits of radiotherapy in patients with lung cancer. Radiation-induced differentiation of lung fibroblasts to myofibroblasts plays a key role in RILI. Recent studies have shown that mesenchymal stem cells (MSCs) can protect against lung fibrosis and that Wnt/β-catenin signaling is involved in fibrotic processes. In the present study, we explored the therapeutic potential of human umbilical cord MSCs (HUMSCs) for preventing radiation-induced differentiation of human lung fibroblasts (HLFs) to myofibroblasts...
2015: Tohoku Journal of Experimental Medicine
Chun-yang Zhang, Yan Zhu, Hua-song Feng, Xu-xin Chen
OBJECTIVE: To investigate the effect of irradiated human lung fibroblasts (HLFs) on the canonical Wnt/β-catenin signaling pathway in human umbilical cord mesenchymal stem cells (HUMSCs). METHODS: HUMSCs were cultured alone (single group) or co-cultured with HLFs exposed to 5Gy X-rays (co-culture group). The protein levels of GSK-3β, p-GSK-3β, FRAT1 and β-catenin in HUMSCs were examined by Western blotting 3 days after culture or co-culture. WISP-1 protein levels in conditioned medium were examined by ELISA...
March 2015: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Jing-Yuan Chuang, Po-Chun Chen, Ching-Wen Tsao, An-Chen Chang, Ming-Yu Lein, Ching-Chia Lin, Shih-Wei Wang, Chiao-Wen Lin, Chih-Hsin Tang
Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by poor prognosis and a low survival rate. VEGF-A is the most established angiogenic factor involved in the angiogenic-regulated tumor progression. WISP-1/CCN4 is an extracellular matrix-related protein that belongs to the Cyr61, CTGF, Nov (CCN) family and regulates many biological functions, such as angiogenesis. Previous studies indicated the role of WISP-1 in tumor progression. However, the angiogenic property of WISP-1 in the cancer microenvironment has never been discussed...
February 28, 2015: Oncotarget
Piotr Sklepkiewicz, Takayuki Shiomi, Rajbir Kaur, Jie Sun, Susan Kwon, Becky Mercer, Peter Bodine, Ralph Theo Schermuly, Isaac George, P Christian Schulze, Jeanine M D'Armiento
BACKGROUND: The Wnt/β-catenin signaling pathway plays a central role during cardiac development and has been implicated in cardiac remodeling and aging. However, the role of Wnt modulators in this process is unknown. In this study, we examined the role of the Wnt signaling inhibitor secreted frizzled-related protein-1 (sFRP-1) in aged wild-type and sFRP-1-deficient mice. METHODS AND RESULTS: sFRP-1 gene deletion mice were grossly normal with no difference in mortality but developed abnormal cardiac structure and dysfunction with progressive age...
March 2015: Circulation. Heart Failure
Sarah Stephens, Joanne Palmer, Irena Konstantinova, Andrew Pearce, Gabor Jarai, Elizabeth Day
Wnt-1 inducible signalling pathway protein 1 (WISP-1/CCN4) is an extracellular matrix protein that belongs to the Cyr61 (cysteine-rich protein 61), CTGF (connective tissue growth factor) and NOV (CCN) family and plays a role in multiple cellular processes. No specific WISP-1 receptors have been identified but emerging evidence suggests WISP-1 mediates its downstream effects by binding to integrins. Here we describe a functional analysis of integrin receptor usage by WISP-1. Truncated WISP-1 proteins were produced using a baculovirus expression system...
March 2015: Journal of Cell Communication and Signaling
Bernard Perbal
The considerable advances of genome sequencing over the past decades have had a profound impact on our daily life and opened up new avenues for the public to have access to their genetic information and learn more about their ancestry, genealogy and other traits that make each of us unique individuals. A very large number of individual single nucleotide polymorphisms (SNPs) have been associated to diseases whereas others have no known phenotype. For example, among the SNPs mapped within ccn1(cyr61), ccn2(ctgf), ccn3(nov), ccn4(wisp-1), ccn5(wisp-2) and ccn6 (wisp-3), only mutations within ccn4 were associated to PPD (the autosomal recessive skeletal disorder Progressive Pseudorheumatoid Dysplasia)...
December 2014: Journal of Cell Communication and Signaling
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