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https://www.readbyqxmd.com/read/28904079/ascorbic-acid-promotes-a-tgf%C3%AE-1-induced-myofibroblast-phenotype-switch
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28720506/arecoline-activates-latent-transforming-growth-factor-%C3%AE-1-via-mitochondrial-reactive-oxygen-species-in-buccal-fibroblasts-suppression-by-epigallocatechin-3-gallate
#7
Yu-Ping Hsieh, King-Jean Wu, Hsin-Ming Chen, Yi-Ting Deng
BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) is a premalignant condition caused by the chewing of areca nut (AN). Transforming growth factor β (TGFβ) plays a central role in the pathogenesis of OSF. Connective tissue growth factor (CTGF or CCN2) and early growth response-1 (Egr-1) are important mediators in the fibrotic response to TGFβ in several fibrotic disorders including OSF. Arecoline, a major AN alkaloid, induced the synthesis of CCN2 and Egr-1 in human buccal mucosal fibroblast (BMFs)...
July 15, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28672855/ginsenoside-rh2-improves-cardiac-fibrosis-via-ppar%C3%AE-stat3-signaling-in-type-1-like-diabetic-rats
#8
Shih-Hsiang Lo, Chao-Tien Hsu, Ho-Shan Niu, Chiang-Shan Niu, Juei-Tang Cheng, Zhih-Cherng Chen
Ginsenoside Rh2 (Rh2) is an active principal ingredient contained in ginseng (Panax ginseng Meyer), a medicinal herb used to enhance health worldwide. The present study is designed to investigate the effect of Rh2 on myocardial fibrosis in diabetic rats. In a streptozotocin-induced model of type-1 diabetic rats (STZ-diabetic rats), the increased fasting blood glucose levels and heart weight/body weight (HW/BW) ratio were substantially alleviated by Rh2. Moreover, Rh2 improved cardiac performance in STZ-diabetic rats...
June 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28610597/anti-connective-tissue-growth-factor-ctgf-ccn2-monoclonal-antibody-attenuates-skin-fibrosis-in-mice-models-of-systemic-sclerosis
#9
Katsunari Makino, Tomoko Makino, Lukasz Stawski, Kenneth E Lipson, Andrew Leask, Maria Trojanowska
BACKGROUND: Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although the involvement of connective tissue growth factor (CTGF/CCN2) has been well-documented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully investigated. Our aim was to examine the therapeutic potential of CTGF blockade in a preclinical model of SSc using two approaches: smooth muscle cell fibroblast-specific deletion of CTGF (CTGF knockout (KO)) or a human anti-CTGF monoclonal antibody, FG-3019...
June 13, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28520806/als-skeletal-muscle-shows-enhanced-tgf-%C3%AE-signaling-fibrosis-and-induction-of-fibro-adipogenic-progenitor-markers
#10
David Gonzalez, Osvaldo Contreras, Daniela L Rebolledo, Juan Pablo Espinoza, Brigitte van Zundert, Enrique Brandan
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28486491/correction-smad3-dependent-ccn2-mediates-fibronectin-expression-in-human-skin-dermal-fibroblasts
#11
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0173191.].
2017: PloS One
https://www.readbyqxmd.com/read/28464379/activation-of-transforming-growth-factor-%C3%AE-1-by-thrombin-via-integrins-%C3%AE-v%C3%AE-1-%C3%AE-v%C3%AE-3-and-%C3%AE-v%C3%AE-5-in-buccal-fibroblasts-suppression-by-epigallocatechin-3-gallate
#12
Jenny Zwei-Chieng Chang, Yu-Ping Hsieh, Wen-Hsin Lin, Hsin-Ming Chen, Mark Yen-Ping Kuo
BACKGROUND: Transforming growth factor-beta (TGF-β) plays a central role in the pathogenesis of oral submucous fibrosis (OSF). Thrombin is a key player in tissue repair, inflammation, and fibrosis after injury. METHODS: Effects of thrombin on activated-TGF-β1 levels, Smad3 phosphorylation, and connective tissue growth factor (CTGF/CCN2) synthesis in primary human buccal mucosal fibroblasts (BMFs) were assessed by enzyme-linked immunosorbent assay or Western blot analysis...
May 2, 2017: Head & Neck
https://www.readbyqxmd.com/read/28463604/nell-1-hmgb1-and-ccn2-enhance-migration-and-vasculogenesis-but-not-osteogenic-differentiation-compared-to-bmp2
#13
Shorouk Fahmy-Garcia, Marjolein van Driel, Janneke Witte-Buoma, Heike Walles, Johannes Ptm van Leeuwen, Gerjo van Osch, Eric Farrell
Currently, autografts still represent the gold standard treatment for the repair of large bone defects. However, these are associated with donor site morbidity, increased pain, cost and recovery time. The ideal therapy would use biomaterials combined with bone growth factors to induce and instruct bone defect repair without the need to harvest patient tissue. In this line, BMPs have been the most extensively used agents for clinical bone repair, but at supraphysiological doses that are not without risk. Because of the need to eliminate the risks of BMP2 use in vivo, we assessed the ability of three putative osteogenic factors, Nell-1, HMGB1 and CCN2, to enhance the essential processes for bone defect repair in vitro and compared them to BMP2...
May 2, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28460443/sphingosine-1-phosphate-promotes-ovarian-cancer-cell-proliferation-by-disrupting-hippo-signaling
#14
Qianlan Fan, Yuan Cheng, Hsun-Ming Chang, Masashi Deguchi, Aaron J Hsueh, Peter C K Leung
Epithelial ovarian carcinomas account for more than 90% of human ovarian cancers and have become the primary cause of death for gynecological malignancies. Unlimited cell proliferation and resistance to cell apoptosis contribute to the development of ovarian cancers. However, the underlying mechanisms involved in these processes in epithelial ovarian carcinomas are yet poorly understood. In the present study, we examined the Hippo signaling gene expression and investigated the effects of Sphingosine 1-phosphate (S1P) on cell proliferation and the underlying mechanisms in human ovarian cancer cell lines, OVCAR3 and SKOV3...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28438434/connective-tissue-growth-factor-decreases-mitochondrial-metabolism-through-ubiquitin-mediated-degradation-of-mitochondrial-transcription-factor-a-in-oral-squamous-cell-carcinoma
#15
Wei-Ting Lai, Yue-Ju Li, Shi-Bei Wu, Cheng-Ning Yang, Tai-Sheng Wu, Yau-Huei Wei, Yi-Ting Deng
BACKGROUND/PURPOSE: Deregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear. METHODS: OSCC cells stably overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were established. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were examined by the Seahorse XF24 analyzer...
April 21, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28433542/blockade-of-pdgf-receptors-by-crenolanib-has-therapeutic-effect-in-patient-fibroblasts-and-in-preclinical-models-of-systemic%C3%A2-sclerosis
#16
Katsunari Makino, Tomoko Makino, Lukasz Stawski, Julio C Mantero, Robert Lafyatis, Robert Simms, Maria Trojanowska
Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment options. Activated fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen and the development of fibrosis. Platelet-derived growth factor (PDGF), a potent mitogen for cells of mesenchymal origin, has been implicated in the activation of SSc fibroblasts. Our aim was to examine the therapeutic potential of crenolanib, an inhibitor of PDGF receptor signaling, in cultured fibroblasts and in angiotensin II-induced skin and heart fibrosis...
August 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28399671/substance-p-increases-ccn2-dependent-on-tgf-beta-yet-collagen-type-i-via-tgf-beta1-dependent-and-independent-pathways-in-tenocytes
#17
Nagat Frara, Paul W Fisher, Yingjie Zhao, Joseph T Tarr, Mamta Amin, Steven N Popoff, Mary F Barbe
Transforming growth factor beta 1 (TGFbeta-1) and connective tissue growth factor (CCN2) are important mediators of tissue repair and fibrosis, with CCN2 functioning as a downstream mediator of TGFβ-1. Substance P (SP) is also linked to collagen production in tenocytes. A link between SP, TGFbeta-1 and CCN2 has yet to be established in tenocytes or fibrogenic processes. We sought to determine whether SP induces tenocyte proliferation, CCN2, or collagen production via TGFbeta-1 signaling or independently in rat primary tenocytes...
March 1, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28371159/transforming-growth-factor-%C3%AE-1-regulates-the-expression-of-ccn2-in-human-keratinocytes-via-smad-erk-signalling
#18
Elizabeth Kiwanuka, Johan Pe Junker, Elof Eriksson
Connective tissue growth factor (CCN2/CTGF) and transforming growth factor β1 (TGF-β1) are important regulators of skin wound healing, but controversy remains regarding their expression in epithelial cell lineages. Here, we investigate the expression of CCN2 in keratinocytes during reepithelialisation and its regulation by TGF-β1. CCN2 was detected in the epidermis of healing full-thickness porcine wounds. Human keratinocytes were incubated with or without 10 ng/ml TGF-β1, and signalling pathways were blocked with 10-μM SIS3 or 20-μM PD98059...
March 29, 2017: International Wound Journal
https://www.readbyqxmd.com/read/28343287/catabolic-effects-of-fgf-1-on-chondrocytes-and-its-possible-role-in-osteoarthritis
#19
Abdellatif El-Seoudi, Tarek Abd El Kader, Takashi Nishida, Takanori Eguchi, Eriko Aoyama, Masaharu Takigawa, Satoshi Kubota
Fibroblast growth factor 1 (FGF-1) is a classical member of the FGF family and is produced by chondrocytes cultured from osteoarthritic patients. Also, this growth factor was shown to bind to CCN family protein 2 (CCN2), which regenerates damaged articular cartilage and counteracts osteoarthritis (OA) in an animal model. However, the pathophysiological role of FGF-1 in cartilage has not been well investigated. In this study, we evaluated the effects of FGF-1 in vitro and its production in vivo by use of an OA model...
March 25, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28330503/caffeine-modulates-glucocorticoid-induced-expression-of-ctgf-in-lung-epithelial-cells-and-fibroblasts
#20
Markus Fehrholz, Kirsten Glaser, Christian P Speer, Silvia Seidenspinner, Barbara Ottensmeier, Steffen Kunzmann
BACKGROUND: Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling. Connective tissue growth factor (CTGF, CCN2) plays a key role in airway remodeling and has been implicated in the pathogenesis of chronic lung diseases such as bronchopulmonary dysplasia (BPD) in preterm infants...
March 23, 2017: Respiratory Research
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