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https://www.readbyqxmd.com/read/27863006/the-role-of-ccn5-wisp2-protein-in-pancreatic-islets
#1
REVIEW
Jun-Li Liu, Nancy Kaddour, Subrata Chowdhury, Qing Li, Zu-Hua Gao
In search of direct targets of IGF-I action, we discovered CCN5/WISP2 as a novel protein expressed in pancreatic β-cells. As a member of Cyr61 (connective tissue growth factor in human), CTGF (cysteine rich 61, in mouse), and Nov (nephroblastoma overexpressed, in chicken) family, IGF-I together with Wnt signaling stimulate its expression. When overexpressed in insulinoma cells, CCN5 promotes cell proliferation and cell survival against streptozotocin-induced cell death. The cell proliferation effect seems to be caused by AKT phosphorylation and increased cyclin D1 level...
November 12, 2016: Journal of Diabetes
https://www.readbyqxmd.com/read/27853940/novel-role-of-ccn3-that-maintains-the-differentiated-phenotype-of-articular-cartilage
#2
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
https://www.readbyqxmd.com/read/27829832/members-of-the-cyr61-ctgf-nov-protein-family-emerging-players-in-hepatic-progenitor-cell-activation-and-intrahepatic-cholangiocarcinoma
#3
Qunfeng Wu, Marda Jorgensen, Joanna Song, Junmei Zhou, Chen Liu, Liya Pi
Hepatic stem/progenitor cells (HPC) reside quiescently in normal biliary trees and are activated in the form of ductular reactions during severe liver damage when the replicative ability of hepatocytes is inhibited. HPC niches are full of profibrotic stimuli favoring scarring and hepatocarcinogenesis. The Cyr61/CTGF/NOV (CCN) protein family consists of six members, CCN1/CYR61, CCN2/CTGF, CCN3/NOV, CCN4/WISP1, CCN5/WISP2, and CCN6/WISP3, which function as extracellular signaling modulators to mediate cell-matrix interaction during angiogenesis, wound healing, fibrosis, and tumorigenesis...
2016: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/27769912/expression-of-fibrosis-related-molecules-in-the-oral-mucosa-of-six-animal-species-a-reference-for-selecting-animal-models
#4
Guoliang Sa, Xuepeng Xiong, Jiangang Ren, Yifang Zhao, Sangang He
Several animal models have been used in studies associated with oral submucous fibrosis (OSF); however, an appropriate model based on the histopathological characteristics of OSF is still needed. This study aimed to provide histological references for selecting a potential model. The expression intensities of collagen type I (Col I), type III (Col III), type IV (Col IV), fibronectin (FN), transforming growth factors β (TGF-β), and connective tissue growth factor (CCN2) in the oral mucosa of the human and six non-human animal species were measured by immunohistochemistry...
October 18, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27766493/ccn2-reduction-mediates-protective-effects-of-bmp7-treatment-in-obstructive-nephropathy
#5
Lucas L Falke, Jan Willem Leeuwis, Karen M Lyons, Christine L Mummery, Tri Q Nguyen, Roel Goldschmeding
Treatment with rhBMP7 exerts profound protective effects in a wide variety of experimental models of renal disease. However, little is known about how these protective effects are mediated, and which cells in the kidney are targeted by exogenous rhBMP7 treatment. To determine if rhBMP7 increases glomerular and tubulointerstitial canonical BMP signaling, we performed Unilateral Ureteral Obstruction (UUO, a widely used obstructive nephropathy model) in mice reporting transcriptional activity downstream of canonical BMP signaling by the expression of GFP under the BMP Responsive Element of the Id1 promoter (BRE:gfp mice)...
October 20, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27761803/the-pivotal-role-of-ccn2-in-mammalian-palatogenesis
#6
Joseph T Tarr, Timothy G Visser, Joanne E Moon, Honey Hendesi, Mary F Barbe, James P Bradley, Steven N Popoff
Mammalian palatogenesis is a complex process involving a temporally and spatially regulated myriad of factors. Together these factors control the 3 vital processes of proliferation, elevation and fusion of the developing palate. In this study, we show for the first time the unequivocally vital role of CCN2 in development of the mammalian palate. We utilized CCN2 knockout (KO) mice and cranial neural crest derived mesenchymal cells from these CCN2 KO mice to investigate the 3 processes crucial to normal palatogenesis...
October 20, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27752926/ccn2-induces-cellular-senescence-in-fibroblasts
#7
Joon-Ii Jun, Lester F Lau
The expression of Ccn2 (CTGF) has been linked to fibrosis in many tissues and pathologies, although its activities in fibroblastic cells and precise mechanism of action in fibrogenesis are still controversial. Here, we showed that CCN2 can induce cellular senescence in fibroblasts both in vitro and in vivo, whereupon senescent cells express an anti-fibrotic "senescence-associated secretory phenotype" (SASP) that includes upregulation of matrix metalloproteinases and downregulation of collagen. Mechanistically, CCN2 induces fibroblast senescence through integrin α6β1-mediated accumulation of reactive oxygen species, leading to activation of p53 and induction of p16(INK4a)...
October 18, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27734404/an-analysis-of-pathological-activities-of-ccn-proteins-in-joint-disorders-mechanical-stretch-mediated-ccn2-expression-in-cultured-meniscus-cells
#8
Takayuki Furumatsu, Toshifumi Ozaki
The multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, also known as connective tissue growth factor, regulates cellular proliferation, differentiation, and tissue regeneration. Recent literatures have described important roles of CCN2 in the meniscus metabolism. However, the mechanical stress-mediated transcriptional regulation of CCN2 in the meniscus remains unclear. The meniscus is a fibrocartilaginous tissue that controls complex biomechanics of the knee joint. Therefore, the injured unstable meniscus has a poor healing potential especially in the avascular inner region...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734403/method-for-analysis-of-matrix-degradation-by-ccn2-through-the-mmp-timp-system
#9
Susan V McLennan, Danqing Min, Xiaoyu Wang, Stephen M Twigg
Many studies have shown effects of members of the CCN family on matrix synthesis and accumulation but few have examined degradative pathways. This scarcity of information is in part due to the lack of suitable model systems. Here we describe methods for making rhCCN2 and also for the preparation of a biosynthetically labeled matrix substrate that can be used to measure the effect of CCN on cellular or secreted degradative pathways.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734402/analysis-of-pathological-activities-of-ccn2-ctgf-in-muscle-dystrophy
#10
María José Acuña, Enrique Brandan
CCN2 or connective tissue growth factor (CTGF) is a matricellular protein that regulates several cellular processes. In skeletal muscle, CTGF is a key modulator of fibrogenesis, is increased in pathological conditions such as muscular dystrophies, and plays a major role in the pathology outcome. Overexpression of CTGF in skeletal muscle of wild-type mice results in muscle damage, fibrosis, and reduction of strength. In contrast, a decrease in CTGF in dystrophic mice increases strength and reduces damage and fibrosis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734398/tgf-%C3%AE-1-and-ccn2-stimulated-sirius-red-assay-for-collagen-accumulation-in-cultured-cells
#11
Philip C Trackman, Debashree Saxena, Manish V Bais
A simple method for the determination of relative levels of insoluble collagen accumulation in fibroblast cultures is presented. Confluent cell cultures are provided with sodium ascorbate which is then permissive for collagen deposition. At intervals, cultures are fixed and stained successively with sirius red and then crystal Violet to, respectively, assess for relative changes in collagen accumulation in response to factors such as TGF-β1 or matricellular CCN2 and changes in DNA content as an index of changes in cell density...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734395/analysis-of-pathological-activities-of-ccn-proteins-in-fibrotic-diseases-kidney-fibrosis
#12
Hideki Yokoi, Masashi Mukoyama
Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis. Transforming growth factor-β (TGF-β) is postulated to play a central role in the development of both fibrotic processes. Extracellular matrix proteins, particularly type I collagen and fibronectin, accumulate in the tissue during renal fibrogenesis. CCN2, also known as connective tissue growth factor (CTGF), is increased in the setting of fibrosis and modulates a number of downstream signaling pathways involved in the fibrogenic properties of TGF-β...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734394/studying-the-ccn-proteins-in-fibrosis
#13
James Hutchenreuther, Andrew Leask, Katherine Thompson
CCN2 is a profibrotic matricellular protein. CCN2 directly promotes cell adhesion and indirectly promotes fibrosis by activating adhesive signaling in response to growth factors, cytokines, and extracellular matrix. The following protocols will allow the direct assessment of other CCN family members in these processes.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734393/ccn2-in-skin-fibrosis
#14
Andrew Leask
CCN2, formerly known as connective tissue growth factor, was discovered in 1991. Soon after its discovery, CCN2 was shown to be upregulated in response to the profibrotic cytokine transforming growth factor (TGF) β and to be constitutively overexpressed in fibrotic conditions. These early observations led to the hypothesis that CCN2 was a key regulator of fibrosis. However, only recently have data been generated that directly demonstrate this hypothesis. This review summarizes these observations and suggests a mechanism of action for CCN2...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734392/analysis-of-transcytosis-of-ccn2-by-chondrocytes
#15
Kazumi Kawata, Satoshi Kubota, Masaharu Takigawa
Transcytosis is a mechanism for the transcellular transport of biomolecules. Analysis of transcytosis is frequently performed in cells with distinct polarity, such as brain endothelial cells. However, in cells without evident polarity, analysis of transcytosis has not been performed. Here, we describe a method for analyzing transcytosis of a CCN family protein through chondrocytic cells having no apparent polarity.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734391/generation-and-analysis-of-cartilage-specific-ccn2-overexpression-in-transgenic-mice
#16
Takako Hattori, Shinsuke Itoh, Masaharu Takigawa
Recent progress in gene-editing technology has provided a strong impact for improved our understanding of molecular functions in living organisms. Here we describe our method to generate transgene-overexpressing mouse models, which method involves the use of tissue-specific promoters for analyzing a certain molecule (s) in special tissues. The protocol described in this chapter uses the Col2a1 promoter-enhancer, which is known for driving specific and strong transgene expression in cartilage and is based on several of our studies showing a positive role of the connective tissue growth factor (CCN2) in cartilage-bone development and maintenance of articular cartilage...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734390/production-and-analysis-of-conditional-ko-mice-of-ccn2-in-kidney
#17
Naohiro Toda, Hideki Yokoi, Kiyoshi Mori, Masashi Mukoyama
CCN2 has been shown to be closely involved in the progression of renal fibrosis, indicating the potential of CCN2 inhibition as a therapeutic target. Although the examination of the phenotypes of adult CCN2 knockout mice with renal diseases has yielded valuable scientific insights, perinatal death has limited studies of CCN2 in vivo. Conditional knockout technology has become widely used for the deletion of genes in the desired cell populations and time points through the use of cell-specific Cre recombinase-expressing mice...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734385/gene-expression-analysis-of-ccn-protein-in-bone-under-mechanical-stress
#18
Teruko Takano-Yamamoto, Tomohiro Fukunaga, Nobuo Takeshita
To investigate mechanical-dependent bone remodeling, we had previously applied various types of mechanical loading onto the teeth of rats and mice. In vitro cultured bone cells were then used to elucidate the mechanisms underlying the specific phenomenon revealed by in vivo experiments. This review describes the techniques used to upregulate CCN2 expression in bone cells produced by different types of mechanical stress, such as fluid shear stress and substrate strain in vitro, and compression or tension force in vivo...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734384/in-vivo-evaluation-of-cartilage-regenerative-effects-of-ccn2-protein
#19
Takashi Nishida, Satoshi Kubota, Masaharu Takigawa
CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a unique growth factor that promotes the proliferation and differentiation, but not the hypertrophy of articular chondrocytes in vitro. Based on these findings, we previously evaluated the cartilage-regenerative effects of recombinant CCN2 protein (rCCN2) by using both mono-iodoacetate (MIA) injection into the rat joint cavity and formation of full-thickness defects of rat articular cartilage in vivo, and our results suggested the utility of CCN2 in the regeneration of articular cartilage...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734382/cell-biological-assays-for-measuring-odontogenic-activities-of-ccn-proteins
#20
Koichiro Muromachi, Hiroshi Sugiya, Nobuyuki Tani-Ishii
In postnatal dentin formation, odontoblast differentiation occurs in the pulp tissue regenerative process under pathological condition. Odontoblasts and newly differentiated odontoblast-like cells beneath the caries lesion form tertiary dentin and are highly odontogenic. To observe the activity of dentinogenesis occur within the hard tissue, a combination of immunohistological analysis and immunodetection of dentinogenesis specific molecules, such as dentin sialophosphoprotein (DSPP) and/or its cleaved products dentin sialoprotein (DSP) and dentin phosphoprotein (DPP), is a reliable approach...
2017: Methods in Molecular Biology
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