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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
I Barchetta, F A Cimini, R De Gioannis, G Ciccarelli, L Bertoccini, A Lenzi, M G Baroni, M G Cavallo
AIMS: Procollagen-III peptide (PIIINP) is a marker of fibrosis associated with increased cardio-metabolic risk and progression of chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH); its association with type 2 diabetes mellitus has not been elucidated yet. Aim of this study was to investigate the relationship between circulating PIIINP levels, metabolic traits and body fat distribution in subjects with T2DM with or without NAFLD. MATERIALS AND METHODS: Data from sixty-two T2DM subjects recruited in our Diabetes outpatient clinics at Sapienza University of Rome, Italy, were analysed...
February 22, 2018: Diabetes/metabolism Research and Reviews
Lillianne H Wright, Daniel J Herr, Symone S Brown, Harinath Kasiganesan, Donald R Menick
Myocardial infarctions (MIs) cause the loss of myocytes due to lack of sufficient oxygenation and latent revascularization. Although the administration of histone deacetylase (HDAC) inhibitors reduces the size of infarctions and improves cardiac physiology in small-animal models of MI injury, the cellular targets of the HDACs, which the drugs inhibit, are largely unspecified. Here, we show that WNT-inducible secreted protein-1 (Wisp-1), a matricellular protein that promotes angiogenesis in cancers as well as cell survival in isolated cardiac myocytes and neurons, is a target of HDACs...
February 22, 2018: JCI Insight
Christopher Tacke, Krasimira Aleksandrova, Miriam Rehfeldt, Veronica Murahovschi, Mariya Markova, Margrit Kemper, Silke Hornemann, Ulrike Kaiser, Caroline Honig, Christiana Gerbracht, Stefan Kabisch, Tina Hörbelt, D Margriet Ouwens, Martin O Weickert, Heiner Boeing, Andreas F H Pfeiffer, Olga Pivovarova, Natalia Rudovich
WNT1 inducible signaling pathway protein 1 (WISP-1/CCN4) is a novel adipokine, which is upregulated in obesity, and induces a pro-inflammatory response in macrophages in-vitro. Preclinical observations suggested WISP-1/CCN4 as a potential candidate for novel obesity therapy targeting adipose tissue inflammation. Whether circulating levels of WISP-1/CCN4 in humans are altered in obesity and/or type 2 diabetes (T2DM) and in the postprandial state, however, is unknown. This study assessed circulating WISP-1/CCN4 levels in a) paired liquid meal tests and hyperinsulinemic- euglycemic clamps (cohort I, n = 26), b) healthy individuals (cohort II, n = 207) and c) individuals with different stages of obesity and glucose tolerance (cohort III, n = 253)...
November 11, 2017: Journal of Cell Communication and Signaling
Miguel Quiros, Hikaru Nishio, Philipp A Neumann, Dorothee Siuda, Jennifer C Brazil, Veronica Azcutia, Roland Hilgarth, Monique N O'Leary, Vicky Garcia-Hernandez, Giovanna Leoni, Mingli Feng, Gabriela Bernal, Holly Williams, Priya H Dedhia, Christian Gerner-Smidt, Jason Spence, Charles A Parkos, Timothy L Denning, Asma Nusrat
In response to injury, epithelial cells migrate and proliferate to cover denuded mucosal surfaces and repair the barrier defect. This process is orchestrated by dynamic crosstalk between immune cells and the epithelium; however, the mechanisms involved remain incompletely understood. Here, we report that IL-10 was rapidly induced following intestinal mucosal injury and was required for optimal intestinal mucosal wound closure. Conditional deletion of IL-10 specifically in CD11c-expressing cells in vivo implicated macrophages as a critical innate immune contributor to IL-10-induced wound closure...
September 1, 2017: Journal of Clinical Investigation
Xiang Zhong, Yue Ju Tu, Yi Li, Ping Zhang, Wei Wang, Sha Sha Chen, Li Li, Arthur Ck Chung, Hui Yao Lan, Hai Yong Chen, Gui Sen Li, Li Wang
WNT1-inducible signaling pathway protein-1 (WISP-1) is an extracellular matrix-related protein that plays multiple roles in cellular physiology and pathology. Accumulating evidence shows that WISP-1 is involved in the process underlying fibrotic diseases. However, the correlation between WISP-1 and renal fibrosis is unknown. In this study, we hypothesized that WISP-1 levels might be correlated with renal fibrosis and could be used as a noninvasive biomarker to screen for renal fibrosis in patients with chronic kidney disease (CKD)...
2017: American Journal of Translational Research
Aristea K Batsali, Charalampos Pontikoglou, Dimitrios Koutroulakis, Konstantia I Pavlaki, Athina Damianaki, Irene Mavroudi, Kalliopi Alpantaki, Elisavet Kouvidi, George Kontakis, Helen A Papadaki
BACKGROUND: In view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton's jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population. METHODS: MSCs were isolated and expanded from BM aspirates of hematologically healthy donors (n = 18) and from the WJ of full-term neonates (n = 18)...
April 26, 2017: Stem Cell Research & Therapy
Hsiao-Chi Tsai, Huey-En Tzeng, Chun-Yin Huang, Yuan-Li Huang, Chun-Hao Tsai, Shih-Wei Wang, Po-Chuan Wang, An-Chen Chang, Yi-Chin Fong, Chih-Hsin Tang
In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood...
April 13, 2017: Cell Death & Disease
Mengmeng Feng, Shuqin Jia
Wnt-1 inducible signaling pathway-1 (WISP-1), also known as CCN-4, belongs to the connective tissue growth factor (CTGF) family. WISP-1 is primarily expressed in embryonic stem cells and is involved in adult organ development. WISP-1 participates in many cellular processes, including proliferation, differentiation, apoptosis and adhesion. In addition, WISP-1 plays an important role in diverse pathophysiological processes, such as embryonic development, inflammation, injury repairs and cancers. Recent studies showed that WISP-1 was highly correlated with tumor progression and malignant transformation, whereas it played an oncogenic role in colorectal cancer, cholangiocarcinoma, hepatocellular carcinoma and breast cancer...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Stephany C Barreto, Amitabha Ray, Page Ag Edgar
The extracellular membrane (ECM) is no longer regarded as inert, rather it has multiple versatile physiologic functions. Its diverse composition is implicated in each step of cancer progression including inflammation, angiogenesis, tumor invasion and metastasis. In addition to structural proteins, the ECM also contains a family of non-structural proteins called matricellular proteins. The six secreted CCN proteins, which belong to the matricellular protein family, include the following: Cyr61 (CCN1), CTGF (CCN2), Nov (CCN3), WISP- 1 (CCN4), WISP-2 (CCN5) and WISP-3(CCN6)...
November 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Hongwei Shao, Long Cai, Mecker Moller, Biju Issac, Leiming Zhang, Mark Owyong, Anna Elizabeth Moscowitz, Roberto Vazquez-Padron, Freddy Radtke, Zhao-Jun Liu
Mesenchymal stem cells-derived fibroblasts (MSC-DF) constitute a significant portion of stromal fibroblasts in the tumor microenvironment (TME) and are key modulators of tumor progression. However, the molecular mechanisms that determine their tumor-regulatory function are poorly understood. Here, we uncover the Notch1 pathway as a molecular determinant that selectively controls the regulatory role of MSC-DF in melanoma metastasis. We demonstrate that the Notch1 pathway's activity is inversely correlated with the metastasis-regulating function of fibroblasts and can determine the metastasis-promoting or -suppressing phenotype of MSC-DF...
November 29, 2016: Oncotarget
Fu-Jun Li, Xin-Juan Wang, Xiao-Li Zhou
BACKGROUND: WISP-1 is a member of the CCN family of growth factors and has been reported to play an important role in tumorigenesis by triggering downstream events via integrin signaling. However, little is known about the role of WISP-1 in proliferation of salivary gland carcinoma (SGC) cells. METHODS: In this study, we investigated the WISP-1 expression in SGC tissues via immunohistochemical staining, Western blotting assay, and real-time quantitative polymerase chain reaction method, and then evaluated the regulatory role of WISP-1 in the growth of SGC A-253 cells...
2016: OncoTargets and Therapy
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...
November 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
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