Редактирование: CCN1

CCN family member 1 precursor (Cellular communication network factor 1) (Cysteine-rich angiogenic inducer 61) (Insulin-like growth factor-binding protein 10) (IBP-10) (IGF-binding protein 10) (IGFBP-10) (Protein CYR61) (Protein GIG1) [CYR61] [GIG1] [IGFBP10]

==Publications==

{{medline-entry
|title=Sodium tanshinone IIA sulfonate restrains fibrogenesis through induction of senescence in mice with induced deep endometriosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32651107
|abstract=Does sodium tanshinone IIA sulfonate ([[STS]]) induce cellular senescence in endometriotic lesions and thus restrict lesional development and fibrogenesis in a recently established mouse model of deep endometriosis? Prospective randomized animal experiment in which deep endometriosis was induced in female Balb/C mice, which were then randomly divided into three groups (low-dose [[STS]], high-dose [[STS]] and inert vehicle control) and received treatment for 2 weeks. All mice were then sacrificed and their lesions excised and harvested. Lesion weight was quantified and all lesion samples were subjected to histochemical analysis of the extent of lesional fibrosis by Masson trichrome staining, and of cellular senescence by senescence-associated β-galactosidase (SA-β-gal), along with immunohistochemistry analyses of p53, [[CCN1]], activate Salvador 1 (Sav1), hyaluronan synthase 2 ([[HAS2]]), survivin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and [[CD163]]-positive M2 macrophages. Plasma P-selectin and hyaluronic acid levels were also quantified. Hotplate testing was also administered before the induction, then before and after treatment. [[STS]] treatment resulted in significantly reduced lesion weight, stalled lesional fibrogenesis and improved hyperalgesia, seemingly through the induction of cellular senescence by activating p53, Sav1 and [[CCN1]] while suppressing [[HAS2]], survivin and GM-CSF, resulting in increased apoptosis and reduced lesional infiltration of alternatively activated macrophages. In addition, [[STS]] treatment significantly reduced the plasma concentration of P-selectin and hyaluronic acid, possibly leading to reduced lesional platelet aggregation. [[STS]] appears to be a promising compound for treating endometriosis. The results suggest that senescence may restrict lesional progression and fibrogenesis, and targeting the senescence pathway may have desirable therapeutic potential.

|keywords=* Deep endometriosis
* Fibrogenesis
* Mouse
* Senescence
* Sodium tanshinone IIA sulfonate
|full-text-url=https://sci-hub.do/10.1016/j.rbmo.2020.04.006
}}
{{medline-entry
|title=Inhibition of cellular communication network factor 1 ([[CCN1]])-driven senescence slows down cartilage inflammaging and osteoarthritis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32622876
|abstract=To explore the role of cellular communication network factor 1 ([[CCN1]]) in cartilage inflammaging and osteoarthritis (OA) pathogenesis in the isolated primary human chondrocytes in vitro, cartilage explants ex vivo, and a pre-clinical mice model. Recombinant human [[CCN1]] stimulation and small interfering RNA inhibition were conducted in human chondrocytes. The RNA was extracted to quantify catabolic targets and pro-inflammatory genes and the proteins were probed with specific antibodies. IL-1β and IL-6 were monitored by ELISA. IHC was performed to evaluate important hypertrophic hallmarks and catabolic markers. The effects of Tanshinone IIA on chondrocytes were investigated in both time-dependent and dose-dependent processes. Cartilage explants were cultured in growth medium and further treated with Tanshinone IIA. The intra-articular injection was performed in 13 months old C57BL/6J mice. Safranin O and fast green staining were performed to evaluate the histological change of cartilage followed by a semi-quantitative analysis using the OARSI scoring system. RNA and protein levels of [[CCN1]] increased in an age-dependent manner compared to young donors. Increased [[CCN1]] expression was also found in the damaged area compared to the non-lesion area which correlated with the advanced pathological change in human OA. The overexpression of [[CCN1]] promoted chondrocytes senescence, while the down-regulation of [[CCN1]] by small interfering RNA reduced [[CCN1]] production and limited inflammation secretion suggesting that [[CCN1]] was a possible novel target to intervene OA. Inhibition of [[CCN1]] by using Tanshinone IIA could reduce SASP components in a dose- and time-dependent manner. Additionally, our data showed that Tanshinone IIA was able to preserve articular cartilage integrity, suppress [[CCN1]] production, and inhibit SASP factors in human cartilage explants and in aged mice model. This study showed that [[CCN1]] signaling aggravated cartilage inflammaing and matrix degradation. Collectively, our findings showed new insight into repurposing Tanshinone IIA for slowing down OA advancement in human and mice by inhibiting the [[CCN1]] axis.

|keywords=* CCN1
* Cartilage inflammaging
* Chondrocyte cluster
* Osteoarthritis
* Senescence
|full-text-url=https://sci-hub.do/10.1016/j.bone.2020.115522
}}
{{medline-entry
|title=[Aging of skin fibroblasts: genetic and epigenetic factors.]
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32160428
|abstract=Gerontocosmetology is the rapid developing knowledge area that has a very large applied meaning. Herewith a lot of information about skin aging and geroprotectors for skin rejuvenation hasn't a scientific background. Thus, understanding the fundamental mechanisms of skin aging becomes the actual task of molecular gerontology. Skin fibroblasts are the polyfunctional cell population that synthesize a number of biologically active substances and participate in maintaining of extracellular matrix homeostasis, skin hydratation and endocrine and immune function. In the review genetic (accumulation of nuclear and mitochondrial DNA mistakes) and epigenetic factors of skin fibroblasts aging are described. Role of AP-1, NF-κB, c-jun, [[CCN1]], TGF-β, [[TNF]]-α, MMP-1, MMP-3, MMP-8, MMP-9 and glycation in skin fibroblasts aging are discussed. There are some data about decreasing of skin fibroblasts ability to migration and synthesis of paxillins and aquaporin-3 (AQP3) during aging. Role of hormonal regulation in skin fibroblasts aging are described. Geroprotective action of melatonin to skin fibroblasts are showed. Reviewed molecular-cellular aspects of skin fibroblasts aging can be take into consideration for scientific background of using of cosmetic products for retarding of skin aging rate.
|mesh-terms=* Cells, Cultured
* Epigenesis, Genetic
* Fibroblasts
* Humans
* Skin Aging
|keywords=* aging
* melatonin
* signal molecules
* skin fibroblasts

}}
{{medline-entry
|title=The senescence-associated matricellular protein [[CCN1]] in plasma of human subjects with idiopathic pulmonary fibrosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31765873
|abstract=Cellular senescence has been linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF). [[CCN1]] is a matricellular protein that has been shown to induce cellular senescence and contribute to lung fibrosis in pre-clinical models. In this report, we determined plasma [[CCN1]] levels in patients with IPF and its potential role in clinical outcomes. We evaluated 88 patients diagnosed with IPF at the University of Alabama at Birmingham. [[CCN1]] levels were measured in plasma specimens by ELISA. The primary outcome measure was transplant-free survival (TFS) duration. High-[[CCN1]] levels were associated with a lower transplant-free survival independent of %FVC and %D CO compared to patients with low plasma [[CCN1]] (HR = 2.15; 95%CI 1.04-4.45, p = 0.04). This study demonstrates that plasma levels of [[CCN1]] may be predictive of survival in IPF. Given the plausible role of [[CCN1]] in cellular senescence and pathobiology of IPF, the predictive value of [[CCN1]] in disease progression among patients with IPF warrants further investigation.
|mesh-terms=* Aged
* Cellular Senescence
* Cysteine-Rich Protein 61
* Disease Progression
* Enzyme-Linked Immunosorbent Assay
* Female
* Humans
* Idiopathic Pulmonary Fibrosis
* Male
* Middle Aged
* Outcome Assessment, Health Care
* Predictive Value of Tests
* Survival Rate
|keywords=* CCN1
* Cellular senescence
* Idiopathic pulmonary fibrosis
* Transplant-free survival
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023981
}}
{{medline-entry
|title=[[CCN1]] (CYR61) and [[CCN3]] (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26744771
|abstract=During placental development, continuous invasion of trophoblasts into the maternal compartment depends on the support of proliferating extravillous trophoblasts (EVTs). Unlike tumor cells, EVTs escape from the cell cycle before invasion into the decidua and spiral arteries. This study focused on the regulation properties of glycosylated and non-glycosylated matricellular [[CCN1]] and [[CCN3]], primarily for proliferation control in the benign SGHPL-5 trophoblast cell line, which originates from the first-trimester placenta. Treating SGHPL-5 trophoblast cells with the glycosylated forms of recombinant [[CCN1]] and [[CCN3]] decreased cell proliferation by bringing about G0/G1 cell cycle arrest, which was accompanied by the upregulation of activated Notch-1 and its target gene p21. Interestingly, both CCN proteins increased senescence-associated β-galactosidase activity and the expression of the senescence marker p16. The migration capability of SGHPL-5 cells was mostly enhanced in response to [[CCN1]] and [[CCN3]], by the activation of FAK and Akt kinase but not by the activation of ERK1/2. In summary, both CCN proteins play a key role in regulating trophoblast cell differentiation by inducing senescence and enhancing migration properties. Reduced levels of [[CCN1]] and [[CCN3]], as found in early-onset preeclampsia, could contribute to a shift from invasive to proliferative EVTs and may explain their shallow invasion properties in this disease.
|mesh-terms=* Biomarkers
* Cell Cycle Checkpoints
* Cell Line
* Cell Movement
* Cell Proliferation
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p16
* Cyclin-Dependent Kinase Inhibitor p21
* Cysteine-Rich Protein 61
* Extracellular Signal-Regulated MAP Kinases
* Focal Adhesion Protein-Tyrosine Kinases
* Humans
* Models, Biological
* Nephroblastoma Overexpressed Protein
* Phosphorylation
* Proto-Oncogene Proteins c-akt
* Receptors, Notch
* Signal Transduction
* Trophoblasts
* Up-Regulation
* beta-Galactosidase
|keywords=* CCN1
* CCN3
* migration
* placenta
* senescence
* trophoblast
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853050
}}
{{medline-entry
|title=Aging increases [[CCN1]] expression leading to muscle senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24196529
|abstract=Using microarray analysis, we found that aging sarcopenia is associated with a sharp increase in the mRNA of the matricellular protein [[CCN1]] (Cyr61/CTGF/Nov). [[CCN1]] mRNA was upregulated 113-fold in muscle of aged vs. young rats. [[CCN1]] protein was increased in aging muscle in both rats (2.8-fold) and mice (3.8-fold). When muscle progenitor cells (MPCs) were treated with recombinant [[CCN1]], cell proliferation was decreased but there was no change in the myogenic marker myoD. However, the [[CCN1]]-treated MPCs did express a senescence marker (SA-βgal). Interestingly, we found [[CCN1]] increased p53, p16(Ink4A), and pRP (hypophosphorylated retinoblastoma protein) protein levels, all of which can arrest cell growth in MPCs. When MPCs were treated with aged rodent serum [[CCN1]] mRNA increased by sevenfold and protein increased by threefold suggesting the presence of a circulating regulator. Therefore, we looked for a circulating regulator. Wnt-3a, a stimulator of [[CCN1]] expression, was increased in serum from elderly humans (2.6-fold) and aged rodents (2.0-fold) compared with young controls. We transduced C2C12 myoblasts with wnt-3a and found that [[CCN1]] protein was increased in a time- and dose-dependent manner. We conclude that in aging muscle, the circulating factor wnt-3a acts to increase [[CCN1]] expression, prompting muscle senescence by activating cell arrest proteins. 
|mesh-terms=* Aging
* Animals
* Cells, Cultured
* Cellular Senescence
* Cysteine-Rich Protein 61
* Gene Expression Regulation
* Humans
* Mice
* Mice, Inbred C57BL
* Muscle, Skeletal
* Myoblasts, Skeletal
* RNA, Messenger
* Rats
* Rats, Inbred F344
* Stem Cells
|keywords=* Cyr61
* RB
* p16ink4a
* p50
* wnt-3a
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919975
}}
{{medline-entry
|title=Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of [[CCN2]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23839921
|abstract=Currently, our ability to treat intervertebral disc ([[IVD]]) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including [[CCN2]], during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in [[IVD]] tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific [[CCN2]] deletion. Expression of CCN proteins was assessed in [[IVD]] tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of [[CCN2]] in notochord-derived tissues, we generated notochord-specific [[CCN2]]-null mice to assess the impact on the [[IVD]] structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), [[IVD]] health was assessed. Loss of the [[CCN2]] gene in notochord-derived cells disrupted the formation of [[IVD]]s in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. [[CCN2]]-knockout mice also had altered expression of [[CCN1]] (Cyr61) and [[CCN3]] (Nov). Mirroring its role during early development, notochord-specific [[CCN2]] deletion accelerated age-associated degeneration of [[IVD]]s. Using a notochord-specific gene targeting strategy, this study demonstrates that [[CCN2]] expression by nucleus pulposus cells is essential to the regulation of [[IVD]] development and age-associated tissue maintenance. The ability of [[CCN2]] to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration.
|mesh-terms=* Aggrecans
* Aging
* Animals
* Collagen Type I
* Collagen Type II
* Connective Tissue Growth Factor
* Disease Models, Animal
* Embryonic Development
* Female
* Intervertebral Disc
* Intervertebral Disc Degeneration
* Magnetic Resonance Imaging
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Notochord

|full-text-url=https://sci-hub.do/10.1002/art.38075
}}
{{medline-entry
|title=The matricellular protein [[CCN1]] suppresses lung cancer cell growth by inducing senescence via the p53/p21 pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23553737
|abstract=[[CCN1]], a secreted matrix-associated molecule, is involved in multiple cellular processes. Previous studies have indicated that expression of [[CCN1]] correlates inversely with the aggressiveness of non-small-cell lung carcinoma (NSCLC); however, the underlying mechanisms remain elusive. Using three NSCLC cell line systems, here we show that long-term treatment of cells with the recombinant [[CCN1]] protein led to a permanent cell cycle arrest in G1 phase; cells remained viable as judged by apoptotic assays. [[CCN1]]-treated NSCLC cells acquired a phenotype characteristic of senescent cells, including an enlarged and flattened cell shape and expression of the senescence-associated β-galactosidase. Immunoblot analysis showed that addition of [[CCN1]] increased the abundance of hypo-phosphorylated Rb, as well as accumulation of p53 and p21. Silencing the expression of p53 or p21 by lentivirus-mediated shRNA production in cells blocked the [[CCN1]]-induced senescence. Furthermore, a [[CCN1]] mutant defective for binding integrin α6β1 and co-receptor heparan sulfate proteoglycans was incapable of senescence induction. Our finding that direct addition of [[CCN1]] induces senescence in NSCLC cells provides a potential novel strategy for therapeutic intervention of lung cancers.
|mesh-terms=* Blotting, Western
* Cell Cycle
* Cell Line, Tumor
* Cell Proliferation
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p21
* Cysteine-Rich Protein 61
* Humans
* Lung Neoplasms
* Signal Transduction
|keywords=* CCN1
* LUNG CANCER
* SENESCENCE
* p21
* p53
|full-text-url=https://sci-hub.do/10.1002/jcb.24557
}}
{{medline-entry
|title=Cysteine-rich protein 61 ([[CCN1]]) domain-specific stimulation of matrix metalloproteinase-1 expression through αVβ3 integrin in human skin fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23504324
|abstract=Human skin largely comprises collagenous extracellular matrix. The hallmark of skin aging is fragmentation of collagen fibrils. Matrix metalloproteinases (MMPs) are largely responsible for collagen degradation. MMP-1, principally derived from dermal fibroblasts, is the major protease capable of initiating degradation of native fibrillar collagens. Presently, we report that [[CCN1]], a secreted and extracellular matrix-associated protein, is elevated in aged human skin dermal fibroblasts in vivo and stimulates MMP-1 expression through functional interaction with αVβ3 integrin in human dermal fibroblasts. [[CCN1]] contains four conserved structural domains. Our results indicate that the three N-terminal domains (IGFBP, VWC, and TSP1), but not the C-terminal CT domain, are required for [[CCN1]] to stimulate MMP-1 expression. This stimulation is dependent on interaction between the active structural domains and αVβ3 integrin. The interaction of VWC domain with integrin αVβ3 is necessary and requires functional cooperation with adjacent IGFBP and TSP1 domains to stimulate MMP-1 expression. Finally, induction of MMP-1 expression in dermal fibroblasts by [[CCN1]] N-terminal domains resulted in fragmentation of type I collagen fibrils in a three-dimensional collagen lattice model. These data suggest that domain-specific interactions of [[CCN1]] with αVβ3 integrin contribute to human skin aging by stimulating MMP-1-mediated collagen fibril fragmentation.
|mesh-terms=* Adult
* Aging
* Collagen Type I
* Cysteine-Rich Protein 61
* Dermis
* Female
* Fibroblasts
* Gene Expression Regulation, Enzymologic
* Humans
* Integrin alphaVbeta3
* Male
* Matrix Metalloproteinase 1
* Protein Structure, Tertiary
* Proteolysis

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636922
}}
{{medline-entry
|title=Matricellular proteins in cardiac adaptation and disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22535894
|abstract=The term matricellular proteins describes a family of structurally unrelated extracellular macromolecules that, unlike structural matrix proteins, do not play a primary role in tissue architecture, but are induced following injury and modulate cell-cell and cell-matrix interactions. When released to the matrix, matricellular proteins associate with growth factors, cytokines, and other bioactive effectors and bind to cell surface receptors transducing signaling cascades. Matricellular proteins are upregulated in the injured and remodeling heart and play an important role in regulation of inflammatory, reparative, fibrotic and angiogenic pathways. Thrombospondin (TSP)-1, -2, and -4 as well as tenascin-C and -X secreted protein acidic and rich in cysteine (SPARC), osteopontin, periostin, and members of the CCN family (including [[CCN1]] and CCN2/connective tissue growth factor) are involved in a variety of cardiac pathophysiological conditions, including myocardial infarction, cardiac hypertrophy and fibrosis, aging-associated myocardial remodeling, myocarditis, diabetic cardiomyopathy, and valvular disease. This review discusses the properties and characteristics of the matricellular proteins and presents our current knowledge on their role in cardiac adaptation and disease. Understanding the role of matricellular proteins in myocardial pathophysiology and identification of the functional domains responsible for their actions may lead to design of peptides with therapeutic potential for patients with heart disease.
|mesh-terms=* Adaptation, Physiological
* Aging
* Animals
* CCN Intercellular Signaling Proteins
* Extracellular Matrix Proteins
* Female
* Heart
* Heart Diseases
* Humans
* Male
* Mice
* Osteopontin
* Rats
* Tenascin
* Thrombospondins
* Ventricular Remodeling

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411042
}}