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https://www.readbyqxmd.com/read/28520806/als-skeletal-muscle-shows-enhanced-tgf-%C3%AE-signaling-fibrosis-and-induction-of-fibro-adipogenic-progenitor-markers
#1
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
#2
(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
#3
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
#4
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
#5
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
#6
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-sclerosis
#7
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. 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 (Ang II)-induced skin and heart fibrosis...
April 19, 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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28326574/tumour-epithelial-and-stromal-characteristics-of-hepatocellular-carcinomas-with-abundant-fibrous-stroma-fibrolamellar-versus-scirrhous-hepatocellular-carcinoma
#12
Young-Joo Kim, Hyungjin Rhee, Jeong Eun Yoo, Venancio A F Alves, Gi Jeong Kim, Hye Min Kim, Paulo Herman, Aline Chagas, Haeryoung Kim, Young Nyun Park
AIMS: The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterized by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. METHODS AND RESULTS: Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for keratin 7 (K7), K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28267785/smad3-dependent-ccn2-mediates-fibronectin-expression-in-human-skin-dermal-fibroblasts
#13
Trupta Purohit, Zhaoping Qin, Chunji Quan, Zhenhua Lin, Taihao Quan
The potential involvement of connective tissue growth factor (CCN2/CTGF) in extracellular matrix (ECM) production is recognized. However, the role CCN2 in fibronectin (FN) gene expression has remained incompletely understood and even controversial. Here we report that CCN2 is absolutely necessary for FN expression in primary human skin dermal fibroblasts, the major cells responsible for ECM production in skin. Gain- and loss-of-function approaches demonstrate that CCN2 is an essential component of FN expression in both basal and stimulation by TGF-β signaling, the major regulator of FN expression...
2017: PloS One
https://www.readbyqxmd.com/read/28208216/msc-derived-ccn2-promotes-the-proliferation-migration-and-invasion-of-human-tongue-squamous-cell-carcinoma-cells
#14
Yu-Ling Wu, Hong-Yu Li, Xiao-Peng Zhao, Jiu-Yang Jiao, Dong-Xiao Tang, Ling-Jian Yan, Quan Wan, Chao-Bin Pan
Recent studies have demonstrated that mesenchymal stem cells (MSCs) exhibit a tropism to tumors and form the tumor stroma. Additionally, we found that MSCs can secrete different types of factors. However, the involvement of MSC-derived factors in human tongue squamous cell carcinoma (TSCC) growth has not been clearly addressed. The CCN family includes multifunctional signaling molecules that affect the initiation and development events of various tumors. In our study, we report that CCN2/connective tissue growth factor (CTGF) was the most highly induced among the CCN family members in MSCs that were co-cultured with TSCC cells...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28183733/neuronal-ctgf-ccn2-negatively-regulates-myelination-in-a-mouse-model-of-tuberous-sclerosis-complex
#15
Ebru Ercan, Juliette M Han, Alessia Di Nardo, Kellen Winden, Min-Joon Han, Leonie Hoyo, Afshin Saffari, Andrew Leask, Daniel H Geschwind, Mustafa Sahin
Disruption of myelination during development has been implicated in a range of neurodevelopmental disorders including tuberous sclerosis complex (TSC). TSC patients with autism display impairments in white matter integrity. Similarly, mice lacking neuronal Tsc1 have a hypomyelination phenotype. However, the mechanisms that underlie these phenotypes remain unknown. In this study, we demonstrate that neuronal TSC1/2 orchestrates a program of oligodendrocyte maturation through the regulated secretion of connective tissue growth factor (CTGF)...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28108312/ctgf-promotes-osteosarcoma-angiogenesis-by-regulating-mir-543-angiopoietin-2-signaling
#16
Li-Hong Wang, Hsiao-Chi Tsai, Yu-Che Cheng, Chih-Yang Lin, Yuan-Li Huang, Chun-Hao Tsai, Guo-Hong Xu, Shih-Wei Wang, Yi-Chin Fong, Chih-Hsin Tang
Osteosarcoma is the most common primary solid tumor of bone. It has a high metastatic potential and occurs predominantly in adolescents and young adults. Angiopoietin 2 (Angpt2) is a key regulator in tumor angiogenesis, facilitating tumor growth and metastasis. Connective tissue growth factor (CTGF, also known as CCN2), is a cysteine-rich protein that has been reported to promote metastasis of osteosarcoma. However, the effect of CTGF on Angpt2 regulation and angiogenesis in human osteosarcoma remains largely unknown...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28039692/biological-characteristics-of-ccn-proteins-in-tumor-development
#17
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
https://www.readbyqxmd.com/read/27916451/progressive-development-of-endometriosis-and-its-hindrance-by-anti-platelet-treatment-in-mice-with-induced-endometriosis
#18
Qi Zhang, Xishi Liu, Sun-Wei Guo
We have recently shown that platelets drive smooth muscle metaplasia (SMM) and fibrogenesis in endometriosis through epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT). To see whether this is true in vivo, this prospective, randomized, and serially evaluated mouse investigation was conducted. Endometriosis was induced in female Balb/C mice, which were then randomly divided into two groups: Tanshinone IIA (TAN) and control (CTL) groups. TAN mice were treated with TAN but CTL mice received none...
February 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/27863006/role-of-ccn5-wnt1-inducible-signaling-pathway-protein-2-in-pancreatic-islets
#19
REVIEW
Jun-Li Liu, Nancy Kaddour, Subrata Chowdhury, Qing Li, Zu-Hua Gao
In search of direct targets of insulin-like growth factor (IGF)-1 action, we discovered CCN5 (WNT1 inducible signaling pathway protein 2 [WISP2]) as a novel protein expressed in pancreatic β-cells. As a member of the "CCN" ( C ysteine-rich angiogenic inducer 61 [Cyr61], C onnective tissue growth factor [CTGF in humans], and N ephroblastoma overexpressed [Nov; in chickens]) family, the expression of CCN5/WISP2 is stimulated by IGF-1 together with Wnt signaling. When overexpressed in insulinoma cells, CCN5 promotes cell proliferation and cell survival against streptozotocin-induced cell death...
November 12, 2016: Journal of Diabetes
https://www.readbyqxmd.com/read/27853940/novel-role-of-ccn3-that-maintains-the-differentiated-phenotype-of-articular-cartilage
#20
Danilo Janune, Tarek Abd El Kader, Eriko Aoyama, Takashi Nishida, Yasuhiko Tabata, Satoshi Kubota, Masaharu Takigawa
Knowledge of the microenvironment of articular cartilage in health and disease is the key to accomplishing fundamental disease-modifying treatments for osteoarthritis. The proteins comprising the CCN Family are matricellular proteins with a remarkable relevance within the context of cartilage metabolism. CCN2 displays a great capability for regenerating articular cartilage, and CCN3 has been shown to activate the expression of genes related to articular chondrocytes and to repress genes related to endochondral ossification in epiphyseal chondrocytes...
November 16, 2016: Journal of Bone and Mineral Metabolism
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