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https://www.readbyqxmd.com/read/29310804/the-cytoskeletal-network-regulates-expression-of-the-profibrotic-genes-pai-1-and-ctgf-in-vascular-smooth-muscle-cells
#1
Rohan Samarakoon, Paul J Higgins
Vascular smooth muscle cells (VSMCs) are subject to changing hemodynamic stimuli that alter cytoskeletal dynamics, cellular architecture, and structure-associated signal transduction. Tensional stress, force application, and structural perturbations are sensed by VSMCs and impact the physiological as well as pathophysiological responses of the vasculature. Microtubule-targeting drugs provide useful tools to analyze cytoskeletal-associated signaling pathways and their linkages to pathological outcomes. Architecture-based controls on a subset of profibrotic genes commonly expressed in vascular disease are highlighted by their frequent induction in mechanically manipulated cells and with associated changes in cytoskeletal dynamics...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29309923/dermal-fibroblast-to-myofibroblast-transition-sustained-by-%C3%AE-v%C3%A3-3-integrin-ilk-snail1-slug-signaling-is-a-common-feature-for-hypermobile-ehlers-danlos-syndrome-and-hypermobility-spectrum-disorders
#2
Nicoletta Zoppi, Nicola Chiarelli, Silvia Binetti, Marco Ritelli, Marina Colombi
Hypermobile Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder with unknown molecular basis mainly characterized by generalized joint hypermobility, joint instability complications and minor skin changes. The phenotypic spectrum is broad and includes multiple associated symptoms shared with chronic inflammatory systemic diseases. The stricter criteria defined in the 2017 EDS nosology leave without an identity many individuals with symptomatic joint hypermobility and/or features of hEDS; for these patients, the term Hypermobility Spectrum Disorders (HSD) was introduced...
January 5, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29289685/tgf-%C3%AE-signalling-pathways-in-different-compartments-of-the-lower-airways-of-stable-copd-patients
#3
Antonino Di Stefano, Claudia Sangiorgi, Isabella Gnemmi, Paolo Casolari, Paola Brun, Fabio Lm Ricciardolo, Marco Contoli, Alberto Papi, Pio Maniscalco, Paolo Ruggeri, Giuseppe Girbino, Francesco Cappello, Stelios Pavlides, Yike Guo, Kian Fan Chung, Peter J Barnes, Ian M Adcock, Bruno Balbi, Gaetano Caramori
BACKGROUND: The expression and localization of transforming growth factor-beta (TGF-β) pathway proteins in different compartments of the lower airways of stable COPD patients is unclear. OBJECTIVE: To determine TGF-β pathway protein expression in patients with stable COPD. METHODS: The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lung of patients with stable COPD (n=44), control smokers with normal lung function (n=24) and control non-smoking subjects (n=11) using immunohistochemistry...
December 28, 2017: Chest
https://www.readbyqxmd.com/read/29219182/the-emerging-role-of-hippo-signaling-pathway-in-regulating-osteoclast-formation
#4
REVIEW
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...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29198711/effects-of-connective-tissue-growth-factor-ctgf-ccn2-on-condylar-chondrocyte-proliferation-migration-maturation-differentiation-and-signalling-pathway
#5
Xin Xing, Zhi Li, Zili Yu, Gu Cheng, Dianqi Li, Zubing Li
CCN2, also known as connective tissue growth factor (CTGF), is a 38 kDa cysteine-rich extracellular matrix protein that regulates a sequence of cellular functions and participates in multiple complex biological processes, such as chondrogenesis and osteogenesis. In the present study, we provided the first evidence describing the physiological role of CCN2 in condylar chondrocyte proliferation, migration, maturation and differentiation. CCN2 was widely expressed throughout the whole layers of condylar cartilage and predominantly distributed in the proliferative zone...
November 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29179163/-the-role-of-osteocytes-in-bone-remodeling
#6
Takashi Nishida, Satoshi Kubota, Masaharu Takigawa
Bone remodeling has important roles in the functions of bone tissues, such as supporting the body and mineral storage. Osteocytes, which are the most abundant cells in bone tissues, detect the mechanical loading and regulate both bone formation by osteoblasts and bone resorption by osteoclasts. However, its mechanism is still unknown. In this review, we summarize how osteocytes detect mechanical stress and discuss the potential role of CCN2/CTGF as a novel bone remodeling factor produced by osteocytes.
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29165602/deletion-of-connective-tissue-growth-factor-ameliorates-peritoneal-fibrosis-by-inhibiting-angiogenesis-and-inflammation
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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