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https://www.readbyqxmd.com/read/29165602/deletion-of-connective-tissue-growth-factor-ameliorates-peritoneal-fibrosis-by-inhibiting-angiogenesis-and-inflammation
#1
Naohiro Toda, Kiyoshi Mori, Masato Kasahara, Kenichi Koga, Akira Ishii, Keita P Mori, Keisuke Osaki, Masashi Mukoyama, Motoko Yanagita, Hideki Yokoi
Background: Connective tissue growth factor (CTGF/CCN2) regulates the signalling of other growth factors and promotes fibrosis. CTGF is increased in mice and humans with peritoneal fibrosis. Inhibition of CTGF has not been examined as a potential therapeutic target for peritoneal fibrosis because systemic CTGF knockout mice die at the perinatal stage. Methods: To study the role of CTGF in peritoneal fibrosis of adult mice, we generated CTGF conditional knockout (cKO) mice by crossing CTGF floxed mice with RosaCreERT2 mice...
November 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29160908/connective-tissue-growth-factor-induces-renal-fibrosis-via-epidermal-growth-factor-receptor-activation
#2
Sandra Rayego-Mateos, José Luis Morgado-Pascual, Raúl R Rodrigues-Diez, Raquel Rodrigues-Diez, Lucas Falke, Sergio Mezzano, Alberto Ortiz, Jesús Egido, Roel Goldschmeding, Marta Ruiz-Ortega
Connective tissue growth factor (CCN2/CTGF) is a matricellular protein overexpressed in progressive human renal diseases, mainly in fibrotic areas. In vitro studies have demonstrated that CCN2 regulates production of extracellular matrix (ECM) proteins and epithelial mesenchymal transition (EMT), and therefore could contribute to renal fibrosis. CCN2 blockade ameliorates experimental renal damage, including diminution of ECM accumulation. We have described that CCN2 and its C-terminal degradation product CCN2(IV), bind to epidermal growth factor receptor (EGFR) to modulate renal inflammation...
November 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29145495/regulatory-mechanism-of-ccn2-production-by-serotonin-5-ht-via-5-ht2a-and-5-ht2b-receptors-in-chondrocytes
#3
Ayaka Hori, Takashi Nishida, Shogo Takashiba, Satoshi Kubota, Masaharu Takigawa
Serotonin (5-hydroxytryptamine: 5-HT) is recognized as a neurotransmitter in the central nerve system and as a regulator of systemic blood pressure in the peripheral tissues. Recently, it was reported that 5-HT2 receptors (5-HT2Rs) were expressed in cartilage tissues lacking both vessels and neurons, suggesting possible novel functions of 5-HT during cartilage development and regeneration. Our previous data indicated that CCN family protein 2/connective tissue growth factor (CCN2/CTGF) plays a central role in cartilage development and regeneration...
2017: PloS One
https://www.readbyqxmd.com/read/29129024/metabolic-regulation-of-the-ccn-family-genes-by-glycolysis-in-chondrocytes
#4
Sho Akashi, Takashi Nishida, Abdellatif El-Seoudi, Masaharu Takigawa, Seiji Iida, Satoshi Kubota
The CCN family consists of 6 genes in the mammalian genome and produces multifunctional proteins involved in a variety of biological processes. Recent reports indicate the profound roles of CCN2 in energy metabolism in chondrocytes, and Ccn2 deficiency is known to alter the expression of 2 other family members including Ccn3. However, almost nothing is known concerning the regulation of the CCN family genes by energy metabolism. In order to gain insight into this critical issue, we initially and comprehensively evaluated the effect of inhibition of glycolysis on the expression of all of the CCN family genes in chondrocytic cells...
November 11, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29110248/why-target-the-tumor-stroma-in-melanoma
#5
REVIEW
James Hutchenreuther, Andrew Leask
Melanoma metastasis is fatal. Melanoma cells are often characterized by an activated extracellular signal-regulated kinase (ERK) pathway downstream of mutations in BRAF. Therapies targeting these BRAF mutations are useful for a while; however, patients ultimately develop resistance to these therapies. Recent evidence suggests that this resistance occurs when tumor cells leave their microenvironment and migrate on a stiff, activated tumor stroma; that is, this resistance is linked to the presence of an extracellular matrix reminiscent of a fibrotic micronvironment...
November 6, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29106524/cardiac-myocyte-%C3%AE-3-adrenergic-receptors-prevent-myocardial-fibrosis-by-modulating-oxidant-stress-dependent-paracrine-signaling
#6
Nerea Hermida, Lauriane Michel, Hrag Esfahani, Emilie Dubois-Deruy, Joanna Hammond, Caroline Bouzin, Andreas Markl, Henri Colin, Anne Van Steenbergen, Christophe De Meester, Christophe Beauloye, Sandrine Horman, Xiaoke Yin, Manuel Mayr, Jean-Luc Balligand
Aims: Human and mouse cardiac beta3-adrenergic receptors (beta3AR) exert antipathetic effects to those of beta1-2AR stimulation. We examined their role in modulating myocardial remodelling, particularly fibrosis in response to haemodynamic stress. Methods and results: Mice with cardiac myocyte-specific expression of beta3AR (ADRB3-tg) or tamoxifen-inducible homozygous deletion (c-Adrb3-ko, with loxP-targeted Adrb3) were submitted to transaortic constriction. A superfusion assay was used for proteomic analysis of paracrine mediators between beta3AR-expressing cardiac myocytes and cardiac fibroblasts cultured separately...
July 6, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29076115/an-early-history-of-ccn2-ctgf-research-the-road-to-ccn2-via-hcs24-ctgf-ecogenin-and-regenerin
#7
REVIEW
Masaharu Takigawa
The principal aim of this historical review is to present the processes by which the different aspects of CCN2/CTGF/Hcs24 were discovered by different groups and how much CCN2/CTGF, by being integrated into CCN family, has contributed to the establishment of the basic concepts regarding the role and functions of this new class of proteins. This review should be particularly useful to new investigators who have recently entered this exciting field of study and also provides a good opportunity to acknowledge the input of those individuals who participated in the development of this scientific field...
October 26, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29067610/regulatory-role-of-mir-18a-to-ccn2-by-tgf-%C3%AE-1-signaling-pathway-in-pulmonary-injury-induced-by-nano-sio2
#8
Hong Yang, Wenchao Li, Yingjian Zhang, Mingyue Li, Ying Gao, Canshan Lao, Bing Shi
This research is designed to investigate the regulatory effect of miR-18a to the target gene connective tissue growth factor (CTGF, or CCN2), by participating in TGF-β1 signaling pathway and explore the pathogenic mechanism of miR-18a in pulmonary injury induced by nano-SiO2 based on our early study. miR-18a and expression of TGF-β1 in Chinese hamster lung (CHL) fibroblasts cells stimulated by supernatants of NR8383 cells exposed to 40 μg/ml nano-SiO2 for 24 h demonstrated 1.58 ± 0.22-fold and 1096...
October 24, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29058957/ctgf-is-expressed-during-cystic-remodeling-in-the-pkd-mhm-cy-rat-model-for-autosomal-dominant-polycystic-kidney-disease-adpkd
#9
Stefan Gauer, Yvonne Holzmann, Bettina Kränzlin, Sigrid C Hoffmann, Norbert Gretz, Ingeborg A Hauser, Margarete Goppelt-Struebe, Helmut Geiger, Nicholas Obermüller
Connective tissue growth factor (CTGF, also named CCN2) plays an important role in the development of tubulointerstitial fibrosis, which most critically determines the progression to end-stage renal failure in autosomal-dominant polycystic kidney disease (ADPKD), the most common genetically caused renal disease. We determined CTGF expression in a well-characterized animal model of human ADPKD, the PKD/Mhm (cy/+) rat. Kidneys of 12 weeks old (cy/+) as well as (+/+) non-affected rats were analyzed for CTGF RNA and protein expression by RT-PCR, Northern and Western blot analyses, in situ hybridization, and IHC...
October 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
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
#10
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/29029514/targeting-of-ccn2-suppresses-tumor-progression-and-improves-chemo-sensitivity-in-urothelial-bladder-cancer
#11
Xiaojing Wang, Tianyuan Xu, Fengbin Gao, Hongchao He, Yu Zhu, Zhoujun Shen
Urothelial bladder cancer (UBC) is the most common urinary neoplasm in China. CCN family protein 2 (CCN2), a cysteine-rich matricellular protein, is abnormally expressed in several cancer types and involved in tumor progression or chemo-resistance. However, detailed expression patterns and effects of CCN2 in UBC still remain unknown. We found that down-regulation of CCN2 suppressed proliferation, migration and invasion of UBC cells in vitro and targeting of CCN2 decelerated xenograft growth in vivo. When treated with mitomycin C (MMC), CCN2-scilencing UBC cells showed lower survival and higher apoptotic rates and these effects were probably mediated via inactivation of Akt and Erk pathways...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29016849/differential-protective-effects-of-connective-tissue-growth-factor-against-a%C3%AE-neurotoxicity-on-neurons-and-glia
#12
Cheng-Ning Yang, Min-Fang Wu, Chung-Chih Liu, Wei-Hung Jung, Yu-Chin Chang, Wang-Pao Lee, Young-Ji Shiao, Chia-Lin Wu, Horng-Huei Liou, Sze-Kwan Lin, Chih-Chiang Chan
Impaired clearance of amyloid-β peptide (Aβ) leads to abnormal extracellular accumulation of this neurotoxic protein that drives neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD patients. However, the role of CTGF in AD pathogenesis remains unclear. Here we characterized the neuroprotective activity of CTGF. We found that CTGF facilitated Aβ uptake and subsequent degradation within primary glia and neuroblastoma cells...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28977597/tgf-%C3%AE-1-inhibits-human-trophoblast-cell-invasion-by-upregulating-connective-tissue-growth-factor-expression
#13
Jung-Chien Cheng, Hsun-Ming Chang, Peter C K Leung
Appropriate trophoblast invasion into the maternal endometrium is essential for successful human implantation and placentation. Connective tissue growth factor (CTGF), also known as CCN2, is a matricellular protein that is expressed in the placenta. Interestingly, the CTGF expression levels in the placenta and serum from patients with severe preeclampsia or fetal growth restriction are higher than those from healthy controls. However, to date, the role of CTGF in the regulation of trophoblast cell invasion remains unclear...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28931920/evaluation-of-circulating-levels-of-ccn2-connective-tissue-growth-factor-in-patients-with-st-elevation-myocardial-infarction
#14
Vibeke Ritschel, Christian Shetelig, Ingebjørg Seljeflot, Shanmuganathan Limalanathan, Pavel Hoffmann, Sigrun Halvorsen, Harald Arnesen, Jan Eritsland, Geir Øystein Andersen
CCN2/Connective tissue growth factor seems to be involved in development of cardiac hypertrophy and fibrosis, but a possible cardioprotective role in left ventricular (LV) remodelling following myocardial infarction has also been suggested. The main objectives of the study were therefore to investigate whether circulating CCN2 levels were associated with infarct size, LV function, adverse remodelling or clinical outcome in two cohorts of patients with ST-elevation myocardial infarction (STEMI). CCN2 was measured in 988 patients 18 hours after PCI and clinical events were recorded after 55 months in the BAMI cohort...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904079/ascorbic-acid-promotes-a-tgf%C3%AE-1-induced-myofibroblast-phenotype-switch
#15
Bram Piersma, Olaf Y Wouters, Saskia de Rond, Miriam Boersema, Rutger A F Gjaltema, Ruud A Bank
l-Ascorbic acid (AA), generally known as vitamin C, is a crucial cofactor for a variety of enzymes, including prolyl-3-hydroxylase (P3H), prolyl-4-hydroxylase (P4H), and lysyl hydroxylase (LH)-mediated collagen maturation. Here, we investigated whether AA has additional functions in the regulation of the myofibroblast phenotype, besides its function in collagen biosynthesis. We found that AA positively influences TGFβ1-induced expression of COL1A1, ACTA2, and COL4A1 Moreover, we demonstrated that AA promotes αSMA stress fiber formation as well as the synthesis and deposition of collagens type I and IV Additionally, AA amplified the contractile phenotype of the myofibroblasts, as seen by increased contraction of a 3D collagen lattice...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28892929/connective-tissue-growth-factor-transgenic-mouse-develops-cardiac-hypertrophy-lean-body-mass-and-alopecia
#16
Edem Nuglozeh
INTRODUCTION: Connective Tissue Growth Factor (CTGF/CCN2) is one of the six members of cysteine-rich, heparin-binding proteins, secreted as modular protein and recognised to play a major function in cell processes such as adhesion, migration, proliferation and differentiation as well as chondrogenesis, skeletogenesis, angiogenesis and wound healing. The capacity of CTGF to interact with different growth factors lends an important role during early and late development, especially in the anterior region of the embryo...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28887614/the-pro-fibrotic-connective-tissue-growth-factor-ctgf-ccn2-correlates-with-the-number-of-necrotic-regenerative-foci-in-dystrophic-muscle
#17
María Gabriela Morales, María José Acuña, Daniel Cabrera, Roel Goldschmeding, Enrique Brandan
Connective tissue growth factor (CTGF/CCN2) has strong inflammatory and profibrotic activities. Its expression is enhanced in skeletal muscular dystrophies such as Duchenne muscular dystrophy (DMD), a myopathy characterized by exacerbated inflammation and fibrosis. In dystrophic tissue, necrotic-regenerative foci, myofibroblasts, newly-regenerated muscle fibers and necrosis all occur simultaneously. To determine if CCN2 is involved in the appearance of the foci, we studied their presence and characteristics in mdx mice (DMD mouse model) compared to mdx mice hemizygous for CCN2 (mdx-Ccn2+/-)...
September 8, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28875415/connective-tissue-growth-factor-ctgf-in-age-related-vascular-pathologies
#18
REVIEW
Zoltan Ungvari, Marta Noa Valcarcel-Ares, Stefano Tarantini, Andriy Yabluchanskiy, Gábor A Fülöp, Tamas Kiss, Anna Csiszar
Connective tissue growth factor (CTGF, also known as CCN2) is a matricellular protein expressed in the vascular wall, which regulates diverse cellular functions including cell adhesion, matrix production, structural remodeling, angiogenesis, and cell proliferation and differentiation. CTGF is principally regulated at the level of transcription and is induced by mechanical stresses and a number of cytokines and growth factors, including TGFβ. In this mini-review, the role of age-related dysregulation of CTGF signaling and its role in a range of macro- and microvascular pathologies, including pathogenesis of aorta aneurysms, atherogenesis, and diabetic retinopathy, are discussed...
September 5, 2017: GeroScience
https://www.readbyqxmd.com/read/28870205/maintenance-of-stemness-is-associated-with-the-interation-of-lrp6-and-heparin-binding-protein-ccn2-autocrined-by-hepatocellular-carcinoma
#19
Qingan Jia, Yang Bu, Zhiming Wang, Bendong Chen, Qiangbo Zhang, Songning Yu, Qingguang Liu
BACKGROUND: The overall response rate of hepatocellular carcinoma (HCC) to chemotherapy is poor. In our previous study, oxaliplatin-resistant HCC is found to exhibit an enhanced stemness, and increased levels of CCN2 and LRP6, while the role of CCN2 and LRP6 in the prognosis of HCC patients, and the interaction regulation mechanism between CCN2 and LRP6 are still unclear. METHODS: The expression levels of CCN2 and LRP6 were detected in large cohorts of HCCs, and functional analyses of CCN2 and LRP6 were performed both in vitro and in vivo...
September 4, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28778066/inhibition-of-lsd1-epigenetically-attenuates-oral-cancer-growth-and-metastasis
#20
Saqer F Alsaqer, Mustafa M Tashkandi, Vinay K Kartha, Ya-Ting Yang, Yazeed Alkheriji, Andrew Salama, Xaralabos Varelas, Maria Kukuruzinska, Stefano Monti, Manish V Bais
Lysine-specific demethylase 1 (LSD1) is a nuclear histone demethylase and a member of the amine oxidase (AO) family. LSD1 is a flavin-containing AO that specifically catalyzes the demethylation of mono- and di-methylated histone H3 lysine 4 through an FAD-dependent oxidative reaction. LSD1 is inappropriately upregulated in lung, liver, brain and esophageal cancers, where it promotes cancer initiation, progression, and metastasis. However, unlike other lysine-specific demethylases, the role and specific targets of LSD1 in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown...
July 27, 2017: Oncotarget
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